OnCo
cancersCancer

Colorectal cancer

The cancer where screening works best and where immunotherapy can make some tumours disappear entirely, yet most metastatic disease still depends on chemotherapy.

Colorectal cancer is the third most common cancer and second leading cause of cancer death worldwide (about 1.9 million cases and 900,000 deaths a year). It is the disease where screening works best: removing adenomas at colonoscopy prevents cancer, and stool and blood tests catch it early. Most cases arise through the adenoma-carcinoma sequence driven by APC loss, KRAS mutation, and TP53 loss (chromosomal instability); about 15% arise through mismatch-repair deficiency (dMMR/MSI-high), either sporadically via MLH1 methylation or through Lynch syndrome. Incidence is rising sharply in adults under 50 for reasons that remain unexplained.

Treatment splits along biology. Localised disease is cured by surgery, with adjuvant FOLFOX or CAPOX for stage III (3 months suffices for low-risk disease) and, since ATOMIC (2025), atezolizumab added for dMMR stage III. Rectal cancer uses total neoadjuvant therapy with chemoradiation and increasingly organ preservation; dMMR rectal cancer can be treated with six months of dostarlimab and no surgery at all (AZUR-1, FDA priority review). Metastatic disease is stratified by RAS, BRAF, HER2, MSI, and sidedness: left-sided RAS/BRAF wild-type tumours get chemotherapy with an EGFR antibody (PARADIGM); others get bevacizumab; BRAF V600E disease gets encorafenib + cetuximab + chemotherapy first line (BREAKWATER, OS doubled to 30 months); KRAS G12C disease gets sotorasib or adagrasib with an EGFR antibody; HER2-amplified disease gets tucatinib + trastuzumab or T-DXd; dMMR disease gets pembrolizumab or nivolumab + ipilimumab first line, with 5-year survival above 50%. Later lines: trifluridine/tipiracil + bevacizumab (SUNLIGHT), fruquintinib (FRESCO-2), regorafenib. Liver-limited metastases are resected or ablated with curative intent in a meaningful minority.

Unsolved: the 95% of metastatic tumours that are microsatellite-stable remain immunotherapy-resistant; KRAS G12D (the commonest mutation) is undrugged; early-onset CRC has no explanation and no screening; ctDNA can identify who will relapse after surgery but no escalation strategy has yet been shown to change that (ALTAIR negative); and anti-EGFR resistance via RAS/EGFR ectodomain clones, MET amplification, and HER2 amplification is universal in metastatic disease.

State of the art today

  • ctDNA-guided adjuvant therapy.
  • Immunotherapy cures in dMMR without surgery.
  • First-line targeted therapy for BRAF V600E.
  • Adjuvant atezolizumab for dMMR stage III colon cancer halves recurrence (ATOMIC, 2025): the first adjuvant IO success in CRC.
  • ctDNA-guided de-escalation is proven (DYNAMIC); blood-based screening is FDA-approved (Shield, 2024) and Medicare-covered.
  • KRAS G12C and HER2 have approved targeted combinations; RAS(ON) inhibitors are entering phase 3 for the remaining KRAS alleles.
Show survival figures (3)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • dMMR disease: immunotherapy first line gives median OS over 6 years (KEYNOTE-177); neoadjuvant IO achieves 68% pCR and 100% 3-year DFS in colon (NICHE-2) and complete organ preservation in rectal cancer (dostarlimab, AZUR-1).
  • BRAF V600E first-line targeted triplet doubled survival to 30 months (BREAKWATER); full approval in 2026.
  • Sidedness plus RAS/BRAF status selects anti-EGFR therapy, yielding median OS near 38 months first line (PARADIGM).
Who it affects
Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • ~1.9 million cases and ~900,000 deaths per year worldwide; third most common cancer, second leading cause of cancer death; incidence rising ~2% per year in adults under 50 in high-income countries.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Colorectum (colon, rectum, anus). World: 1,926,425 new cases, 904,019 deaths.

#CountryNew casesDeaths
1China517,106240,010
2United States of America160,18654,614
3Japan145,75660,473
4Russian Federation83,69341,447
5India70,03840,993
6Germany62,54426,544
7Brazil60,11828,884
8Italy54,78424,188
9France (metropolitan)51,63621,218
10United Kingdom49,42922,868

Standard of care

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Screening

Colonoscopy, FIT, Cologuard, Shield blood test from age 45.

NCCN Guidelines: Colon Cancer
Shield
Stage II-III

Surgery; adjuvant chemotherapy guided by risk and (in trials) ctDNA; exercise programme.

NCCN Guidelines: Colon Cancer
DYNAMICSignateraExercise & lifestyle oncology
Metastatic, MSS

Doublet/triplet chemotherapy + biologic by genotype; targeted combinations for BRAF, KRAS G12C, HER2.

NCCN Guidelines: Colon Cancer
EncorafenibSotorasibAdagrasibTucatinib
Metastatic, dMMR

Checkpoint inhibitors; organ preservation in rectal cancer.

NCCN Guidelines: Colon Cancer
PembrolizumabNivolumabDostarlimab
Screening (average risk, age 45-75)

Colonoscopy every 10 years, annual FIT, multitarget stool DNA every 3 years, CT colonography, or the Shield blood test every 3 years; start at 45 (USPSTF 2021). Lynch carriers: colonoscopy every 1-2 years from age 20-25.

NCCN · NCCN Colorectal Cancer Screening
Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)ShieldFaecal immunochemical test (FIT)Lynch syndrome
Stage I-II colon

Surgical resection; observation for stage I and low-risk stage II. High-risk stage II (T4, obstruction, <12 nodes, LVI): consider 3-6 months fluoropyrimidine ± oxaliplatin; ctDNA-negative patients can safely omit (DYNAMIC). dMMR stage II derives no benefit from 5-FU alone.

DYNAMICCAPOX (capecitabine, oxaliplatin)MRD / molecular residual disease testing
Stage III colon, pMMR

Resection then adjuvant CAPOX for 3 months (T1-3 N1, low risk) or FOLFOX/CAPOX for 6 months (T4 or N2), per IDEA.

NCCN · Category 1
FOLFOX (5-FU, leucovorin, oxaliplatin)CAPOX (capecitabine, oxaliplatin)
Stage III colon, dMMR

Resection then FOLFOX + atezolizumab for 12 months (ATOMIC, 3-year DFS 86% vs 77%). Neoadjuvant nivolumab + ipilimumab (NICHE-2) is an alternative under evaluation.

ATOMIC (Alliance A021502)NICHE-2AtezolizumabFOLFOX (5-FU, leucovorin, oxaliplatin)
Locally advanced rectal, pMMR

Total neoadjuvant therapy: short-course radiation or long-course chemoradiation plus FOLFOX/CAPOX, then TME surgery or watch-and-wait for clinical complete response (OPRA). Non-operative management for select cCR.

IMRT / IGRT (modern external beam)FOLFOX (5-FU, leucovorin, oxaliplatin)Clinical complete response (cCR)
Locally advanced rectal, dMMR

Dostarlimab monotherapy for 6 months with organ preservation (MSK cohort 100% cCR; AZUR-1 registrational, PDUFA February 2027). Chemoradiation and surgery reserved for non-responders.

AZUR-1DostarlimabClinical complete response (cCR)
Metastatic, dMMR/MSI-high, first line

Pembrolizumab (KEYNOTE-177) or nivolumab + ipilimumab (CheckMate 8HW, PFS 54 months); nivolumab monotherapy alternative. Chemotherapy reserved for IO-refractory disease.

NCCN · Category 1 (pembrolizumab, nivolumab + ipil…ESMO-MCBS · 4 (pembrolizumab)
KEYNOTE-177CheckMate 8HWPembrolizumabNivolumabIpilimumab
Metastatic, RAS/BRAF wild-type, left-sided

FOLFOX or FOLFIRI + panitumumab or cetuximab (PARADIGM OS 37.9 months); bevacizumab if anti-EGFR contraindicated. Maintenance fluoropyrimidine ± biologic after induction.

PARADIGMCRYSTAL & FIRE-3PanitumumabCetuximabFOLFOX (5-FU, leucovorin, oxaliplatin)FOLFIRI (5-FU, leucovorin, irinotecan)Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC
Metastatic, RAS-mutant or right-sided (non-G12C)

FOLFOX, FOLFIRI, or FOLFOXIRI + bevacizumab; anti-EGFR contraindicated. KRAS G12D and other alleles: RAS(ON) inhibitors in trials.

BevacizumabFOLFOX (5-FU, leucovorin, oxaliplatin)FOLFIRI (5-FU, leucovorin, irinotecan)Daraxonrasib
Metastatic, BRAF V600E

First line: encorafenib + cetuximab + mFOLFOX6 or FOLFIRI (BREAKWATER, OS 30.3 vs 15.1 months). Later line: encorafenib + cetuximab (BEACON).

BREAKWATEREncorafenibCetuximabFOLFOX (5-FU, leucovorin, oxaliplatin)FOLFIRI (5-FU, leucovorin, irinotecan)
Metastatic, KRAS G12C

Sotorasib + panitumumab (CodeBreaK 300) or adagrasib + cetuximab after chemotherapy; first-line trials ongoing.

CodeBreaK 300SotorasibAdagrasibPanitumumabCetuximabKRAS G12C inhibitor + anti-EGFR antibody (colorectal)
Metastatic, HER2-amplified, RAS wild-type

Tucatinib + trastuzumab (MOUNTAINEER) or trastuzumab deruxtecan 5.4 mg/kg (DESTINY-CRC02) after chemotherapy; MOUNTAINEER-03 tests first-line use.

MOUNTAINEER & MOUNTAINEER-03DESTINY-CRC02TucatinibTrastuzumabTrastuzumab deruxtecan
Metastatic, refractory (third line and beyond)

Trifluridine/tipiracil + bevacizumab (SUNLIGHT, OS 10.8 months), then fruquintinib (FRESCO-2) or regorafenib; NTRK inhibitor if fusion; clinical trials.

SUNLIGHTFRESCO-2Trifluridine/tipiracilFruquintinibRegorafenibBevacizumab
Oligometastatic liver or lung disease

Resection, thermal ablation, or SBRT with curative intent after multidisciplinary review; perioperative chemotherapy; 5-year survival 30-50% after complete resection of liver metastases.

Thermal ablation (RFA, microwave, cryo)SBRT / SABR (stereotactic radiotherapy)Robotic & minimally invasive surgery

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test
  • RAS (KRAS/NRAS)
  • BRAF V600E
  • MSI/dMMR
  • HER2
  • NTRK
  • sidedness
  • ctDNA MRD
  • RAS (KRAS and NRAS exons 2-4) for anti-EGFR eligibility
  • MMR/MSI status (universal testing at diagnosis)
  • HER2 amplification (IHC/ISH or NGS)
  • Primary tumour sidedness
  • NTRK fusions (rare)
  • POLE/POLD1 (ultramutated, IO-responsive)
  • ctDNA MRD after surgery (Signatera, Guardant Reveal)
  • CEA (monitoring)
  • UGT1A1*28 (irinotecan dosing) and DPYD (fluoropyrimidine toxicity)
  • Germline testing for Lynch when dMMR or young onset

Target prevalence in this cancer

Target / alterationPrevalenceSource
EGFR
Benefit restricted to RAS/BRAF wild-type (~40%)
100%
Wikipedia
CEACAM5
80-90%
Wikipedia
TP53
55-60%
cBioPortal (TCGA)
KRAS
G12C ~3-4%
40-45%
cBioPortal (TCGA)
PIK3CA / PI3K-alpha
15-20%
cBioPortal (TCGA)
WRN helicase (MSI-high cancers)
15%
BRAF
8-12%
cBioPortal (TCGA)
HER2
RAS wild-type enriched
3-5%
Wikipedia
NTRK
Enriched in MSI-high
<1%
Wikipedia
VEGF / VEGFR
n/a
Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 19575-Fluorouracil synthesised

    Heidelberger; still the backbone of colorectal chemotherapy 70 years later.

    Cytotoxic chemotherapy
  2. 1988Vogelstein's adenoma-carcinoma sequence

    APC → KRAS → TP53 model of colorectal tumorigenesis defines the genetic paradigm of cancer.

    KRASTP53Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center
  3. 1990MOSAIC and the adjuvant era; Lynch syndrome genes identified (1993)

    Adjuvant 5-FU/levamisole shown to improve survival in stage III (1990); MSH2/MLH1 cloned 1993.

    Lynch syndrome
  4. 2000Irinotecan and oxaliplatin combinations

    FOLFIRI and FOLFOX double median metastatic survival from ~12 to ~20 months.

    FOLFOX (5-FU, leucovorin, oxaliplatin)FOLFIRI (5-FU, leucovorin, irinotecan)
  5. 2004Bevacizumab and cetuximab approved
  6. 2004Bevacizumab and cetuximab approved

    First anti-angiogenic and first anti-EGFR antibodies; MOSAIC establishes adjuvant FOLFOX.

    BevacizumabCetuximabFOLFOX (5-FU, leucovorin, oxaliplatin)
  7. 2008KRAS mutation predicts anti-EGFR failure

    Retrospective CRYSTAL/OPUS analyses; first negative predictive biomarker in CRC; RAS testing becomes mandatory.

    CRYSTAL & FIRE-3KRAS
  8. 2014Extended RAS and sidedness

    FIRE-3 and CALGB 80405 subgroups show anti-EGFR benefit only in left-sided RAS wild-type tumours.

    Sidedness (left vs right colon)CRYSTAL & FIRE-3
  9. 2015Consensus molecular subtypes; trifluridine/tipiracil approved

    CMS1-4 classification; RECOURSE establishes TAS-102 in refractory disease.

    Consensus molecular subtypes (CMS1-4)Trifluridine/tipiracil
  10. 2017Pembrolizumab for MSI-high tumours
    Pembrolizumab
  11. 2017Pembrolizumab: first tumour-agnostic approval, dMMR

    Based on KEYNOTE-016/164 and others; dMMR CRC becomes the model immunotherapy-responsive GI tumour.

    PembrolizumabMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Tumour-agnostic (tissue-agnostic) approval
  12. 2018IDEA: 3 months of adjuvant CAPOX suffices for low-risk stage III
    CAPOX (capecitabine, oxaliplatin)
  13. 2020KEYNOTE-177: chemotherapy-free first line for dMMR; BEACON: encorafenib + cetuximab for BRAF
    KEYNOTE-177Encorafenib
  14. 2022Dostarlimab: 100% complete response in dMMR rectal cancer
    Dostarlimab
  15. 2022Dostarlimab: 100% complete responses in dMMR rectal cancer; PARADIGM; DYNAMIC

    Organ preservation without surgery (Cercek, NEJM); panitumumab beats bevacizumab in left-sided disease; ctDNA-guided de-escalation.

    DostarlimabPARADIGMDYNAMIC
  16. 2023SUNLIGHT and FRESCO-2 expand late-line options; tucatinib + trastuzumab first HER2 regimen; NICHE-2 pCR 68%
    SUNLIGHTFRESCO-2MOUNTAINEER & MOUNTAINEER-03NICHE-2
  17. 2024Shield: first blood test for CRC screening
    Shield
  18. 2024Shield blood test approved for screening; BREAKWATER accelerated approval; CheckMate 8HW
    ShieldBREAKWATERCheckMate 8HW
  19. 2025ATOMIC: adjuvant atezolizumab for dMMR stage III; sotorasib + panitumumab approved; CHALLENGE exercise trial
    ATOMIC (Alliance A021502)CodeBreaK 300Exercise & lifestyle oncology
  20. 2026BREAKWATER full approval; first-line BRAF targeted therapy
    Encorafenib
  21. 2026BREAKWATER FOLFIRI cohort and full approval; AZUR-1 priority review; T-DXd and RAS(ON) inhibitors advance
    BREAKWATERAZUR-1Daraxonrasib

Pipeline

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Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
EstablishedTumour-informed ctDNA MRD test
Signatera
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib
ApprovedADC
Trastuzumab deruxtecan · Enhertu
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
ApprovedBlood-based colorectal cancer screening test
Shield
AZUR-1MOUNTAINEER & MOUNTAINEER-03CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)CheckMate 8HWctDNA-guided adjuvant therapy as the default in stage II-III colon cancerMaking microsatellite-stable colorectal cancer immunotherapy-responsiveNeoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancerColorectal cancer screening (colonoscopy, FIT, stool DNA, blood)

Open problems

  • MSS metastatic disease is immunotherapy-resistant.
  • Early-onset CRC causes unknown.
  • KRAS G12D (most common) undrugged.
  • Microsatellite-stable metastatic disease (95%) remains immunotherapy-resistant; liver metastases actively suppress systemic immunity.
  • KRAS G12D and G12V, the most common drivers, have no approved inhibitor; RAS(ON) inhibitors are the first credible attempt.
  • Early-onset colorectal cancer is rising ~2% per year with no established cause and no screening before 45.
  • ctDNA identifies who will relapse but no escalation strategy has changed outcomes (ALTAIR negative).
  • Anti-EGFR resistance is universal; rechallenge and ctDNA-guided sequencing are unproven in phase 3.
  • Rectal cancer organ preservation lacks randomised comparison against surgery in pMMR disease.
  • Peritoneal metastases respond poorly to systemic therapy; HIPEC with oxaliplatin failed (PRODIGE 7).
  • Disparities: screening uptake and outcomes differ sharply by race, income, and geography.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Colorectal cancer
condition: Colorectal cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

Add-AspirinALASCCAATOMIC (Alliance A021502)AZUR-1BREAKWATERCHALLENGE (CCTG CO.21)CheckMate 8HWCIRCULATE-Japan (GALAXY / VEGA / ALTAIR)CodeBreaK 300CRYSTAL & FIRE-3DESTINY-CRC02DYNAMICFRESCO-2KEYNOTE-177MOUNTAINEER & MOUNTAINEER-03NICHE-2PARADIGMPonsegromab phase 2 in cancer cachexiaPREHAB: multimodal prehabilitation before colorectal cancer surgerySUNLIGHT

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Colorectal cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 54 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example RAS, BRAF V600E, MSI/dMMR, HER2, NTRK), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Chromosomal instability / APC-KRAS-TP53 pathway, Mismatch-repair deficient / MSI-high, Lynch syndrome.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Screening

  1. For my situation (screening), which of the standard options do you recommend and why?
    Why: Guideline options include: Colonoscopy, FIT, Cologuard, Shield blood test from age 45.
  2. Am I a candidate for Shield, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Stage II-III

  1. For my situation (stage ii-iii), which of the standard options do you recommend and why?
    Why: Guideline options include: Surgery; adjuvant chemotherapy guided by risk and (in trials) ctDNA; exercise programme.
  2. Am I a candidate for Signatera, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DYNAMIC apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, MSS

  1. For my situation (metastatic, mss), which of the standard options do you recommend and why?
    Why: Guideline options include: Doublet/triplet chemotherapy + biologic by genotype; targeted combinations for BRAF, KRAS G12C, HER2.
  2. Am I a candidate for Encorafenib, Sotorasib, Adagrasib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, dMMR

  1. For my situation (metastatic, dmmr), which of the standard options do you recommend and why?
    Why: Guideline options include: Checkpoint inhibitors; organ preservation in rectal cancer.
  2. Am I a candidate for Pembrolizumab, Nivolumab, Dostarlimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Screening (average risk, age 45-75)

  1. For my situation (screening (average risk, age 45-75)), which of the standard options do you recommend and why?
    Why: Guideline options include: Colonoscopy every 10 years, annual FIT, multitarget stool DNA every 3 years, CT colonography, or the Shield blood test every 3 years; start at 45 (USPSTF 2021). Lynch carriers: colonoscopy every 1-2 years from age 20-25.
  2. Am I a candidate for Shield, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Stage I-II colon

  1. For my situation (stage i-ii colon), which of the standard options do you recommend and why?
    Why: Guideline options include: Surgical resection; observation for stage I and low-risk stage II. High-risk stage II (T4, obstruction, <12 nodes, LVI): consider 3-6 months fluoropyrimidine ± oxaliplatin; ctDNA-negative patients can safely omit (DYNAMIC). dMMR stage II derives no benefit from 5-FU alone.
  2. Am I a candidate for CAPOX (capecitabine, oxaliplatin), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of DYNAMIC apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Stage III colon, pMMR

  1. For my situation (stage iii colon, pmmr), which of the standard options do you recommend and why?
    Why: Guideline options include: Resection then adjuvant CAPOX for 3 months (T1-3 N1, low risk) or FOLFOX/CAPOX for 6 months (T4 or N2), per IDEA.
  2. Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), CAPOX (capecitabine, oxaliplatin), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Stage III colon, dMMR

  1. For my situation (stage iii colon, dmmr), which of the standard options do you recommend and why?
    Why: Guideline options include: Resection then FOLFOX + atezolizumab for 12 months (ATOMIC, 3-year DFS 86% vs 77%). Neoadjuvant nivolumab + ipilimumab (NICHE-2) is an alternative under evaluation.
  2. Am I a candidate for Atezolizumab, FOLFOX (5-FU, leucovorin, oxaliplatin), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of ATOMIC (Alliance A021502) and NICHE-2 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Locally advanced rectal, pMMR

  1. For my situation (locally advanced rectal, pmmr), which of the standard options do you recommend and why?
    Why: Guideline options include: Total neoadjuvant therapy: short-course radiation or long-course chemoradiation plus FOLFOX/CAPOX, then TME surgery or watch-and-wait for clinical complete response (OPRA). Non-operative management for select cCR.
  2. Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Locally advanced rectal, dMMR

  1. For my situation (locally advanced rectal, dmmr), which of the standard options do you recommend and why?
    Why: Guideline options include: Dostarlimab monotherapy for 6 months with organ preservation (MSK cohort 100% cCR; AZUR-1 registrational, PDUFA February 2027). Chemoradiation and surgery reserved for non-responders.
  2. Am I a candidate for Dostarlimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of AZUR-1 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, dMMR/MSI-high, first line

  1. For my situation (metastatic, dmmr/msi-high, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab (KEYNOTE-177) or nivolumab + ipilimumab (CheckMate 8HW, PFS 54 months); nivolumab monotherapy alternative. Chemotherapy reserved for IO-refractory disease.
  2. Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of KEYNOTE-177 and CheckMate 8HW apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, RAS/BRAF wild-type, left-sided

  1. For my situation (metastatic, ras/braf wild-type, left-sided), which of the standard options do you recommend and why?
    Why: Guideline options include: FOLFOX or FOLFIRI + panitumumab or cetuximab (PARADIGM OS 37.9 months); bevacizumab if anti-EGFR contraindicated. Maintenance fluoropyrimidine ± biologic after induction.
  2. Am I a candidate for Panitumumab, Cetuximab, FOLFOX (5-FU, leucovorin, oxaliplatin) or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of PARADIGM and CRYSTAL & FIRE-3 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, RAS-mutant or right-sided (non-G12C)

  1. For my situation (metastatic, ras-mutant or right-sided (non-g12c)), which of the standard options do you recommend and why?
    Why: Guideline options include: FOLFOX, FOLFIRI, or FOLFOXIRI + bevacizumab; anti-EGFR contraindicated. KRAS G12D and other alleles: RAS(ON) inhibitors in trials.
  2. Am I a candidate for Bevacizumab, FOLFOX (5-FU, leucovorin, oxaliplatin), FOLFIRI (5-FU, leucovorin, irinotecan) or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, BRAF V600E

  1. For my situation (metastatic, braf v600e), which of the standard options do you recommend and why?
    Why: Guideline options include: First line: encorafenib + cetuximab + mFOLFOX6 or FOLFIRI (BREAKWATER, OS 30.3 vs 15.1 months). Later line: encorafenib + cetuximab (BEACON).
  2. Am I a candidate for Encorafenib, Cetuximab, FOLFOX (5-FU, leucovorin, oxaliplatin) or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of BREAKWATER apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, KRAS G12C

  1. For my situation (metastatic, kras g12c), which of the standard options do you recommend and why?
    Why: Guideline options include: Sotorasib + panitumumab (CodeBreaK 300) or adagrasib + cetuximab after chemotherapy; first-line trials ongoing.
  2. Am I a candidate for Sotorasib, Adagrasib, Panitumumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CodeBreaK 300 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, HER2-amplified, RAS wild-type

  1. For my situation (metastatic, her2-amplified, ras wild-type), which of the standard options do you recommend and why?
    Why: Guideline options include: Tucatinib + trastuzumab (MOUNTAINEER) or trastuzumab deruxtecan 5.4 mg/kg (DESTINY-CRC02) after chemotherapy; MOUNTAINEER-03 tests first-line use.
  2. Am I a candidate for Tucatinib, Trastuzumab, Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of MOUNTAINEER & MOUNTAINEER-03 and DESTINY-CRC02 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, refractory (third line and beyond)

  1. For my situation (metastatic, refractory (third line and beyond)), which of the standard options do you recommend and why?
    Why: Guideline options include: Trifluridine/tipiracil + bevacizumab (SUNLIGHT, OS 10.8 months), then fruquintinib (FRESCO-2) or regorafenib; NTRK inhibitor if fusion; clinical trials.
  2. Am I a candidate for Trifluridine/tipiracil, Fruquintinib, Regorafenib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of SUNLIGHT and FRESCO-2 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Oligometastatic liver or lung disease

  1. For my situation (oligometastatic liver or lung disease), which of the standard options do you recommend and why?
    Why: Guideline options include: Resection, thermal ablation, or SBRT with curative intent after multidisciplinary review; perioperative chemotherapy; 5-year survival 30-50% after complete resection of liver metastases.

Any stage

  1. Are there clinical trials I could join, for example of Daraxonrasib, Autogene cevumeran, Signatera, AZUR-1?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “MSS metastatic disease is immunotherapy-resistant”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Early-onset CRC causes unknown”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

449top

Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

51
Alcohol reduction, pricing and cancer warning labelsAnti-angiogenic therapyAntibody-drug conjugate (ADC)Aspirin for cancer prevention and adjuvant therapyBariatric surgery and cancer incidenceBispecific antibodiesBreath and volatile-organic-compound detectionCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCancer interception vaccinesChemoprevention & risk-reducing surgeryCoffee and tea intakeColorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Comprehensive genomic profilingCytotoxic chemotherapyDietary supplements during cancer treatment: interactions and harmsEnhanced recovery (ERAS) and perioperative nutritionExercise & lifestyle oncologyExercise during chemotherapy and radiotherapyFasting and fasting-mimicking diets around chemotherapyGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHIPEC / PIPAC (intraperitoneal chemotherapy)Immune checkpoint inhibitorsImmunonutrition before cancer surgeryIMRT / IGRT (modern external beam)Intraoperative radiotherapy (IORT)KRAS & RAS inhibitorsLiquid biopsy (ctDNA)Liver transplantation for cancer (Milan criteria and beyond)Mediterranean and plant-forward dietary patternsMonoclonal antibodiesMRD / molecular residual disease testingMulti-cancer early detection (MCED)Off-the-shelf cancer vaccinesPersonalised neoantigen (mRNA) vaccinesPlatinum agentsPrehabilitation before cancer surgeryRadioembolisation (TARE / SIRT, yttrium-90)Red and processed meat reductionRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Sleep and circadian interventions in cancerSmall-molecule kinase inhibitorsStructured exercise programmes after curative treatmentSystematic drug repurposingTargeting the tumour's own microbesThermal ablation (RFA, microwave, cryo)Time-restricted eating in cancer prevention and survivorshipTopoisomerase-I inhibitors (and ADC payloads)Ultra-processed food and sugar-sweetened drinksVitamin D and omega-3 supplementation

targets

17
ALKBRAFCEACAM5CTLA-4EGFREpCAMHER2KITKRASNTRKPD-1PD-L1RETROS1TP53VEGF / VEGFRWRN helicase (MSI-high cancers)

drugs

38
ApprovedSmall-molecule inhibitor (KRAS G12C)
Adagrasib · Krazati
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
Not mapped hereCytotoxic regimen
CAPOX (capecitabine, oxaliplatin)
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
ApprovedMonoclonal antibody (anti-PD-1)
Dostarlimab · Jemperli
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
ApprovedSmall-molecule kinase inhibitor (BRAF)
Encorafenib · Braftovi
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereCytotoxic regimen
FOLFIRI (5-FU, leucovorin, irinotecan)
Not mapped hereCytotoxic regimen
FOLFOX (5-FU, leucovorin, oxaliplatin)
ApprovedSmall-molecule kinase inhibitor (VEGFR1-3)
Fruquintinib · Fruzaqla
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
Phase 1Small-molecule non-covalent KRAS G12D inhibitor
MRTX1133
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
Not mapped hereThird-generation platinum (DACH-platinum)
Oxaliplatin · Eloxatin
ApprovedMonoclonal antibody (anti-EGFR)
Panitumumab · Vectibix
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3Bispecific antibody (EGFR × LGR5)
Petosemtamab
ApprovedMonoclonal antibody (anti-VEGFR2)
Ramucirumab · Cyramza
ApprovedSmall-molecule multi-kinase inhibitor
Regorafenib · Stivarga
ApprovedBlood-based colorectal cancer screening test
Shield
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu
ApprovedCytotoxic chemotherapy (oral nucleoside)
Trifluridine/tipiracil · Lonsurf
ApprovedSmall-molecule kinase inhibitor (HER2)
Tucatinib · Tukysa
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib

companies

34
AkesoAmgenAstraZenecaBayerBioNTechBoston ScientificBristol Myers SquibbDaiichi SankyoEli Lilly (incl. Loxo)Elicio TherapeuticsExact Sciences (Abbott)FreenomeFrontier MedicinesGenmabGritstone bioGSKGuardant HealthIpsenMerck & Co. (MSD)MerusNateraNouscomPfizer (incl. Seagen)Quanta TherapeuticsRecursion PharmaceuticalsRevolution MedicinesRoche / GenentechSanofiServierSirtex MedicalSummit TherapeuticsTaiho Pharmaceutical (Otsuka)TakedaXilis

institutions

101
A.C. Camargo Cancer CenterAichi Cancer CenterAlliance for Clinical Trials in OncologyAtrium Health Wake Forest Baptist Comprehensive Cancer CenterAuckland City Hospital / Te Pūriri o Te Ora Cancer and Blood ServiceAustralasian Gastro-Intestinal Trials GroupAustrian Breast & Colorectal Cancer Study GroupBeatson West of Scotland Cancer Centre / CRUK Scotland InstituteCanadian Cancer Trials Group (CCTG)Cancer Care Alberta (Alberta Health Services)Cancer Council AustraliaCancer Grand ChallengesCancer Institute of Iran, Imam Khomeini Hospital ComplexCase Comprehensive Cancer CenterChampalimaud Foundation – Champalimaud Clinical CentreChao Family Comprehensive Cancer Center, UC IrvineCleveland Clinic Abu DhabiComprehensive Cancer Center Freiburg (CCCF)Comprehensive Cancer Center Vienna – Medical University of Vienna / AKHEdinburgh Cancer Centre / CRUK Scotland CentreFirst Affiliated Hospital of Sun Yat-sen UniversityHamad Medical Corporation / National Center for Cancer Care and ResearchHo Chi Minh City Oncology HospitalHospital de Clínicas de Porto AlegreHospital del Mar / Hospital del Mar Research InstituteHospital Universitari i Politècnic La FeHunan Cancer HospitalHuntsman Cancer Institute, University of UtahHUS Comprehensive Cancer Center, Helsinki University HospitalINCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaInstitut National d'Oncologie, RabatInstitut Salah AzaïezInstitute of Oncology LjubljanaInstituto Alexander FlemingInstituto Português de Oncologia de Lisboa Francisco GentilInstituto Português de Oncologia do Porto Francisco GentilIstituto di Candiolo IRCCS – FPOIstituto Nazionale Tumori IRCCS Fondazione G. PascaleIstituto Oncologico Veneto IRCCSJohns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterKaiser Permanente Division of ResearchKeio University HospitalKing Faisal Specialist Hospital and Research CentreKing Hussein Cancer CenterKorean Cancer Study GroupLeeds Cancer Centre, St James's University HospitalLeiden University Medical CenterMaria Skłodowska-Curie National Research Institute of OncologyMarkey Cancer Center, University of KentuckyMasaryk Memorial Cancer InstituteMax Delbrück Center for Molecular MedicineMayo Clinic Comprehensive Cancer Center – ArizonaMemorial Sloan Kettering Cancer CenterMUSC Hollings Cancer CenterNational Cancer Center HospitalNational Cancer Center Hospital EastNational Cancer Center KoreaNational Cancer Centre SingaporeNational Institute of Oncology, HungaryNational Taiwan University HospitalNCT/UCC Dresden – University Hospital Carl Gustav CarusNetherlands Cancer Institute (NKI-AvL)NSABP FoundationOlivia Newton-John Cancer Wellness and Research CentreOntario Institute for Cancer ResearchOsaka International Cancer InstituteOslo University Hospital – The Norwegian Radium HospitalOxford Cancer – Oxford University Hospitals and University of OxfordPeking University Cancer HospitalPrince of Wales Hospital / Chinese University of Hong KongRamathibodi Hospital, Mahidol UniversityRambam Health Care CampusRosalind and Morris Goodman Cancer Institute, McGill UniversityRoyal Adelaide HospitalSahlgrenska University Hospital / Sahlgrenska Center for Cancer ResearchShaare Zedek Medical CenterShizuoka Cancer CenterSidney Kimmel Comprehensive Cancer Center at Jefferson HealthTaipei Veterans General HospitalTawam HospitalTel Aviv Sourasky Medical CenterThe Ottawa Hospital Cancer Centre / Ottawa Hospital Research InstituteTohoku University HospitalTUM Klinikum rechts der Isar / CCC MünchenUMC Utrecht Cancer CenterUNICANCERUniversity Cancer Center Mainz (UCT Mainz) / Universitätsmedizin MainzUniversity Hospitals Birmingham / University of Birmingham Cancer Research CentreUniversity of Arizona Cancer CenterUniversity of Malaya Medical CentreUniversity of Wisconsin Carbone Cancer CenterUppsala University Hospital / Uppsala UniversityUSC Norris Comprehensive Cancer CenterUZ Leuven / Leuven Cancer InstituteVanderbilt-Ingram Cancer CenterVelindre Cancer CentreWalter and Eliza Hall Institute of Medical ResearchWeizmann Institute of ScienceWellcome Sanger InstituteWest Japan Oncology GroupZhongshan Hospital, Fudan University

pathways

7
Field cancerisationMicrobiome–tumour interactionsPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)VEGF angiogenesisWnt / β-catenin

terms

19
AdenocarcinomaAdolescent and young adult (AYA) oncologyAlcohol-attributable cancerCirculating tumour DNA (ctDNA)Clinical complete response (cCR)Consensus molecular subtypes (CMS1-4)Faecal immunochemical test (FIT)Glycaemic index and glycaemic loadLGR5Lynch syndromeMetabolic syndrome and insulin resistanceMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Minimal / molecular residual disease (MRD)Neoadjuvant / adjuvant / perioperativeObesity-related cancers (IARC list of 13)Peritoneal metastasisSidedness (left vs right colon)Tumour markerTumour-agnostic (tissue-agnostic) approval

trials

20
Add-AspirinALASCCAATOMIC (Alliance A021502)AZUR-1BREAKWATERCHALLENGE (CCTG CO.21)CheckMate 8HWCIRCULATE-Japan (GALAXY / VEGA / ALTAIR)CodeBreaK 300CRYSTAL & FIRE-3DESTINY-CRC02DYNAMICFRESCO-2KEYNOTE-177MOUNTAINEER & MOUNTAINEER-03NICHE-2PARADIGMPonsegromab phase 2 in cancer cachexiaPREHAB: multimodal prehabilitation before colorectal cancer surgerySUNLIGHT

pairings

5
Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRCBRAF inhibitor + MEK inhibitorctDNA MRD → adjuvant therapy decisionKRAS G12C inhibitor + anti-EGFR antibody (colorectal)Neoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancer

roadmaps

1
KRAS roadmap: undruggable → G12C → pan-RAS

ideas

80
A biomarker-directed trial of vitamin D after surgery for digestive tract cancersA blood test for the pre-metastatic nicheA cheap old tablet to restore appetiteA dietitian in every gastrointestinal and head and neck tumour boardA dose-finding trial for exercise after cancerA frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approvalA funded programme of organ-preservation trials to avoid radical surgeryA national residual-disease weather service: serial blood tests for every curatively treated patient, pooledA prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compressionA public fund and label pathway to trial generic drugs against cancerA randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancersA ring-fenced metastasis programme with metastasis-specific endpointsA test to tell true oligometastatic disease from hidden widespread spreadA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeA video-based surgical quality registry linking assessed skill to cancer outcomesAutomated combination discovery: patient-sample screens feeding Bayesian platform trialsAutomatic germline testing for every cancer type where it changes careBank three spatially separate tumour blocks from every resectionBorrow from past control arms to shrink the control group in phase 3Break the neutrophil DNA nets that catch tumour cells after surgeryCancer interception vaccines for high-risk carriersCancer warnings on alcohol labels, evaluated as a natural experimentCheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stressCombine the new anti-wasting antibody with exercise and proteinConfirm or refute the harm of antioxidant supplements during chemotherapyControlled feeding trials to separate ultra-processing from caloriesCovalent chemistry for the RAS mutations that still have no drugctDNA-guided adjuvant therapy as the default in stage II-III colon cancerDose chemotherapy by muscle mass, not body surface areaEngineered bacteria that live in tumours and manufacture drugs thereEvaluate alcohol minimum unit pricing against cancer incidenceFactorial trials that test several cheap generics at once in the adjuvant settingFour weeks of training and nutrition before major cancer surgery, as standardGet biomarker-directed aspirin after colorectal surgery into labels and guidelinesGet every Lynch syndrome carrier onto the right dose of aspirinGrow each trial patient's tumour as organoids to decide which platform arm opens nextKeep a freshly removed tumour alive on a pump and test drugs in itLink bariatric and GLP-1 registries to cancer registries in every country that has bothLook for the resistant sub-population before the first doseMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumoursMaking microsatellite-stable colorectal cancer immunotherapy-responsiveMandatory staged registries for new surgical techniques before wide adoptionMatch therapy to the type of scar-forming cell in the tumourMechanically pulverise one tumour with ultrasound to wake the immune systemMetastasis prevention as a formal indication with its own trials and regulatory pathwayMultimodal prehabilitation for older patients before major cancer surgeryOff-the-shelf KRAS vaccines after pancreatic cancer surgeryOff-the-shelf natural killer cells to sweep up residual diseaseOffer the blood test for bowel cancer only to people who refuse stool tests or colonoscopyOncology teams order germline tests; tele-genetic counsellors handle the resultsPatent-free open-source development of repurposed and off-patent cancer drugsPathologists order genomic profiling automatically at diagnosis of advanced cancerPay for supervised exercise the way we pay for drugsPerioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgeryPersonalised stool-test cut-offs by age, sex and prior resultsPersonalised vaccines given only when the blood test turns positivePopulation germline screening for hereditary cancer genes with cascade testingPre-consented cohorts that can be randomised to future trials (TwiCs)Reprogramme suppressive macrophages instead of trying to delete themReprogramme the liver's own immune cells to refuse metastasesRisk-stratified follow-up: low-risk survivors to primary care with fast re-entrySexual health assessed and treated as a standard toxicity domainSMART designs to test treatment strategies, not just single drugsSocial impact bonds for cancer prevention, repaid from avoided treatment costsStanding reflex biomarker panels per tumour type, run without an oncologist's orderStrip the platelet coat off travelling tumour cells in ctDNA-positive patientsStructured exercise prescribed like a drug in all curative-intent cancer careStructured mentorship so district general surgeons perform common cancer operations safelyTest DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhereTrain the bone marrow to make better anti-tumour immune cellsTreat insomnia in survivors and measure whether the cancer noticesTwo-week pre-operative windows to compare combination biology head to headUnmask hidden antigens with a short epigenetic course before immunotherapyUpfront reduced-dose regimens tested head-to-head in frail older patientsUse a polygenic risk score to set when screening startsUse pre-surgery immunotherapy windows as the field's biomarker engineUse tumour DNA in blood to decide when to pause treatment in metastatic cancerWhen the blood test is positive, hunt for the lesion with sensitive imagingWRN inhibitors: a second synthetic-lethal win for mismatch-repair cancersZebrafish avatars for a drug answer within a week

collections

1
Colorectal Cancer Alliance

people

41
Alan P. VenookAndrea CercekAndrés CervantesBert VogelsteinCarsten BokemeyerChadwick BosemanCharles D. BlankeDame Deborah JamesDavid CunninghamDongsheng TuDung T. LeElena ÉlezEric R. FearonFeng WangFrank McCormickHagen F. KenneckeHermann BrennerJaime FeliuJin LiJosep TaberneroKatie CouricKenneth W. KinzlerKevan M. ShokatLuis A. Diaz Jr.Matthew MeyersonMyriam ChalabiPaulo HoffPeter J. O'DwyerRené BernardsRui-Hua XuRyan B. CorcoranSang Joon ShinSemir BeyazStephen SuttonSteven A. RosenbergTae Won KimTae-You KimTakayuki YoshinoTanios Bekaii-SaabVincenzo ValentiniVolker Heinemann

bottlenecks

15
AI that is built but not validated or deployedCold tumours and the immunosuppressive microenvironmentDormant cells and minimal residual diseaseFragmented care and guideline gapsInherited risk is mostly unidentifiedKnowledge reaches practice too slowlyMetastasis is understood least and studied lastMisinformation and unproven therapiesMost lethal cancers are found lateNo incentive to repurpose cheap drugsNo one can predict who responds to immunotherapyOlder and multimorbid patients are excluded and undertreatedPreclinical models that do not predict peoplePrevention we already have is not deployedThe undruggable drivers

key papers

19
Alcohol caused an estimated 741,000 cancers worldwide in 2020BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancerCAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 yearsCercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiencyCHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancerCodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancerDostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapyDYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancerFirst trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancersGALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfoldIARC verdict: excess body fat causes 13 cancersKEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancerLe 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organLe 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approvalMinnesota trial: a yearly stool blood test cuts bowel cancer deaths by a thirdNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNordICC: inviting people to a screening colonoscopy reduced bowel cancer, but less than expectedOstrem and Shokat: the hidden pocket that made KRAS G12C druggable

Key papers

19top
rctNew England Journal of Medicine 2025changed practice
BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer

Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.

rctNew England Journal of Medicine 2025changed practice
CHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancer

For colon cancer survivors, a prescribed, supported exercise programme is now an evidence-based treatment with a survival benefit comparable to many drugs. Health systems will need to fund exercise consultants as they fund chemotherapy. The trial does not tell us whether unsupervised advice achieves the same.

rctNew England Journal of Medicine 2024changed practice
NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients

For colon cancer that is mismatch-repair deficient (about 10-15% of colon cancers, more in older patients), a single short course of immunotherapy before surgery is now a reasonable standard and is far more effective than chemotherapy, which barely works in this subtype. It requires testing every colon cancer for mismatch repair at diagnosis, before surgery. Whether some patients can safely skip surgery, as in dMMR rectal cancer, is the next question.

translationalNew England Journal of Medicine 2024changed practice
NICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patients

NICHE-2 shows that a month of immunotherapy before surgery can effectively cure locally advanced dMMR colon cancer, where chemotherapy after surgery has limited benefit. It is changing guidelines towards neoadjuvant checkpoint blockade for this group and raises the question of whether surgery can be omitted altogether, as in dMMR rectal cancer. Whether the same applies to MMR-proficient tumours is being tested but is not established.

rctNew England Journal of Medicine 2023changed practice
CodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancer

Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone barely works in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.

observationalNature Medicine 2023
GALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfold

The blood test stratifies risk far better than stage or pathology. It supports treating ctDNA-positive patients and suggests ctDNA-negative patients gain little from chemotherapy, but because treatment was not randomised the de-escalation claim needs the randomised trials that are now under way.

translationalNew England Journal of Medicine 2022changed practice
Cercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency

Cercek's dostarlimab study is the clearest demonstration that immunotherapy can replace surgery in a solid tumour: patients with dMMR rectal cancer can keep their rectum and avoid the permanent effects of pelvic radiotherapy and surgery. Non-operative management after PD-1 blockade is now in guidelines for this group, and MMR testing before treatment of rectal cancer is essential. The approach applies only to the 5-10% of rectal cancers that are dMMR.

rctNew England Journal of Medicine 2022changed practice
Dostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapy

Patients with rectal cancer whose tumour is mismatch-repair deficient (about 5-10% of rectal cancers) can now be offered immunotherapy alone with the realistic expectation of avoiding surgery, radiotherapy and a permanent stoma. This requires mismatch repair testing on the diagnostic biopsy, close endoscopic and MRI surveillance, and treatment in an experienced centre. It does not apply to the 90% of rectal cancers that are mismatch-repair proficient.

rctNew England Journal of Medicine 2022changed practice
DYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancer

For stage II colon cancer, where most patients are cured by surgery alone, a blood test can identify the minority who benefit from chemotherapy and spare everyone else its side effects. It does not yet prove that treating ctDNA-positive patients improves survival compared with not treating them.

rctNew England Journal of Medicine 2022
NordICC: inviting people to a screening colonoscopy reduced bowel cancer, but less than expected

A colonoscopy probably does reduce bowel cancer risk for the person who has it, but a programme that offers colonoscopy achieves much less if most people decline. Programmes based on stool tests with high uptake may deliver as much population benefit at lower cost and risk.

observationalLancet Oncology 2021
Alcohol caused an estimated 741,000 cancers worldwide in 2020

There is no safe level of alcohol for cancer risk, and the risk is highest for cancers of the mouth, throat, oesophagus, liver, bowel and breast. Public awareness is low; most people do not know alcohol causes breast cancer. Warning labels and minimum pricing are the policy levers being debated.

rctThe Lancet 2020changed practice
CAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 years

People with Lynch syndrome should be offered daily aspirin, which roughly halves bowel cancer risk with a delayed and durable effect. Whether a lower dose (as tested in CAPP3) is as effective, and whether the finding extends to the general population, are separate questions.

translationalClinical Cancer Research 2020
First trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancers

Because Lynch syndrome tumours make the same abnormal proteins in almost every patient, a single vaccine could in principle be given to carriers before cancer develops. This small trial showed the concept is safe and immunogenic; whether it prevents cancer requires the randomised trials now being planned.

rctNew England Journal of Medicine 2020changed practice
KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer

Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of colorectal cancers that are mismatch-repair proficient.

translationalScience 2017changed practice
Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval

This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.

reviewNew England Journal of Medicine 2016changed practice
IARC verdict: excess body fat causes 13 cancers

Maintaining a healthy weight is now established cancer prevention for over a dozen cancer types. For clinicians and policymakers, obesity belongs alongside tobacco and alcohol in prevention strategy. Whether intentional weight loss in adulthood reverses risk is still being studied, including in trials of GLP-1 drugs.

translationalNew England Journal of Medicine 2015changed practice
Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ

This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.

basicNature 2013
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable

The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.

rctNew England Journal of Medicine 1993changed practice
Minnesota trial: a yearly stool blood test cuts bowel cancer deaths by a third

A cheap home stool test, repeated yearly or every two years and followed by colonoscopy when positive, prevents bowel cancer deaths. This is what national bowel screening programmes do today, with FIT replacing the older guaiac test.

Latest papers

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Connected

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technologies

43
Alcohol reduction, pricing and cancer warning labelsAnti-angiogenic therapyAspirin for cancer prevention and adjuvant therapyBariatric surgery and cancer incidenceBreath and volatile-organic-compound detectionCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCancer interception vaccinesChemoprevention & risk-reducing surgeryCoffee and tea intakeColorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Cytotoxic chemotherapyDietary supplements during cancer treatment: interactions and harmsEnhanced recovery (ERAS) and perioperative nutritionExercise & lifestyle oncologyExercise during chemotherapy and radiotherapyFasting and fasting-mimicking diets around chemotherapyGermline (hereditary) testingGLP-1 receptor agonists and obesity-related cancer riskHIPEC / PIPAC (intraperitoneal chemotherapy)Immune checkpoint inhibitorsImmunonutrition before cancer surgeryIMRT / IGRT (modern external beam)Intraoperative radiotherapy (IORT)KRAS & RAS inhibitorsLiver transplantation for cancer (Milan criteria and beyond)Mediterranean and plant-forward dietary patternsMonoclonal antibodiesMRD / molecular residual disease testingMulti-cancer early detection (MCED)Off-the-shelf cancer vaccinesPrehabilitation before cancer surgeryRadioembolisation (TARE / SIRT, yttrium-90)Red and processed meat reductionRobotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)Sleep and circadian interventions in cancerStructured exercise programmes after curative treatmentSystematic drug repurposingTargeting the tumour's own microbesThermal ablation (RFA, microwave, cryo)Time-restricted eating in cancer prevention and survivorshipUltra-processed food and sugar-sweetened drinksVitamin D and omega-3 supplementation

targets

12
BRAFCEACAM5CTLA-4EGFREpCAMHER2KRASNTRKPD-1TP53VEGF / VEGFRWRN helicase (MSI-high cancers)

drugs

38
ApprovedSmall-molecule inhibitor (KRAS G12C)
Adagrasib · Krazati
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
Phase 2Personalised mRNA neoantigen vaccine
Autogene cevumeran
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
Not mapped hereCytotoxic regimen
CAPOX (capecitabine, oxaliplatin)
ApprovedMonoclonal antibody (anti-EGFR)
Cetuximab · Erbitux
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
ApprovedMonoclonal antibody (anti-PD-1)
Dostarlimab · Jemperli
Phase 2Off-the-shelf lymph-node-targeted KRAS peptide vaccine
ELI-002 7P
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
ApprovedSmall-molecule kinase inhibitor (BRAF)
Encorafenib · Braftovi
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
Not mapped hereFluoropyrimidine antimetabolite
Fluorouracil (5-FU) · Adrucil / Efudex
Not mapped hereCytotoxic regimen
FOLFIRI (5-FU, leucovorin, irinotecan)
Not mapped hereCytotoxic regimen
FOLFOX (5-FU, leucovorin, oxaliplatin)
ApprovedSmall-molecule kinase inhibitor (VEGFR1-3)
Fruquintinib · Fruzaqla
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
Phase 1Small-molecule non-covalent KRAS G12D inhibitor
MRTX1133
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
Not mapped hereThird-generation platinum (DACH-platinum)
Oxaliplatin · Eloxatin
ApprovedMonoclonal antibody (anti-EGFR)
Panitumumab · Vectibix
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
Phase 3Bispecific antibody (EGFR × LGR5)
Petosemtamab
ApprovedMonoclonal antibody (anti-VEGFR2)
Ramucirumab · Cyramza
ApprovedSmall-molecule multi-kinase inhibitor
Regorafenib · Stivarga
ApprovedBlood-based colorectal cancer screening test
Shield
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu
ApprovedCytotoxic chemotherapy (oral nucleoside)
Trifluridine/tipiracil · Lonsurf
ApprovedSmall-molecule kinase inhibitor (HER2)
Tucatinib · Tukysa
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib

companies

23
AmgenBayerBoston ScientificBristol Myers SquibbEli Lilly (incl. Loxo)Exact Sciences (Abbott)FreenomeFrontier MedicinesGritstone bioGSKGuardant HealthMerck & Co. (MSD)NateraNouscomPfizer (incl. Seagen)Quanta TherapeuticsRecursion PharmaceuticalsRoche / GenentechServierSirtex MedicalTaiho Pharmaceutical (Otsuka)TakedaXilis

institutions

101
A.C. Camargo Cancer CenterAichi Cancer CenterAlliance for Clinical Trials in OncologyAtrium Health Wake Forest Baptist Comprehensive Cancer CenterAuckland City Hospital / Te Pūriri o Te Ora Cancer and Blood ServiceAustralasian Gastro-Intestinal Trials GroupAustrian Breast & Colorectal Cancer Study GroupBeatson West of Scotland Cancer Centre / CRUK Scotland InstituteCanadian Cancer Trials Group (CCTG)Cancer Care Alberta (Alberta Health Services)Cancer Council AustraliaCancer Grand ChallengesCancer Institute of Iran, Imam Khomeini Hospital ComplexCase Comprehensive Cancer CenterChampalimaud Foundation – Champalimaud Clinical CentreChao Family Comprehensive Cancer Center, UC IrvineCleveland Clinic Abu DhabiComprehensive Cancer Center Freiburg (CCCF)Comprehensive Cancer Center Vienna – Medical University of Vienna / AKHEdinburgh Cancer Centre / CRUK Scotland CentreFirst Affiliated Hospital of Sun Yat-sen UniversityHamad Medical Corporation / National Center for Cancer Care and ResearchHo Chi Minh City Oncology HospitalHospital de Clínicas de Porto AlegreHospital del Mar / Hospital del Mar Research InstituteHospital Universitari i Politècnic La FeHunan Cancer HospitalHuntsman Cancer Institute, University of UtahHUS Comprehensive Cancer Center, Helsinki University HospitalINCLIVA Biomedical Research Institute / Hospital Clínico Universitario de ValenciaInstitut National d'Oncologie, RabatInstitut Salah AzaïezInstitute of Oncology LjubljanaInstituto Alexander FlemingInstituto Português de Oncologia de Lisboa Francisco GentilInstituto Português de Oncologia do Porto Francisco GentilIstituto di Candiolo IRCCS – FPOIstituto Nazionale Tumori IRCCS Fondazione G. PascaleIstituto Oncologico Veneto IRCCSJohns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterKaiser Permanente Division of ResearchKeio University HospitalKing Faisal Specialist Hospital and Research CentreKing Hussein Cancer CenterKorean Cancer Study GroupLeeds Cancer Centre, St James's University HospitalLeiden University Medical CenterMaria Skłodowska-Curie National Research Institute of OncologyMarkey Cancer Center, University of KentuckyMasaryk Memorial Cancer InstituteMax Delbrück Center for Molecular MedicineMayo Clinic Comprehensive Cancer Center – ArizonaMemorial Sloan Kettering Cancer CenterMUSC Hollings Cancer CenterNational Cancer Center HospitalNational Cancer Center Hospital EastNational Cancer Center KoreaNational Cancer Centre SingaporeNational Institute of Oncology, HungaryNational Taiwan University HospitalNCT/UCC Dresden – University Hospital Carl Gustav CarusNetherlands Cancer Institute (NKI-AvL)NSABP FoundationOlivia Newton-John Cancer Wellness and Research CentreOntario Institute for Cancer ResearchOsaka International Cancer InstituteOslo University Hospital – The Norwegian Radium HospitalOxford Cancer – Oxford University Hospitals and University of OxfordPeking University Cancer HospitalPrince of Wales Hospital / Chinese University of Hong KongRamathibodi Hospital, Mahidol UniversityRambam Health Care CampusRosalind and Morris Goodman Cancer Institute, McGill UniversityRoyal Adelaide HospitalSahlgrenska University Hospital / Sahlgrenska Center for Cancer ResearchShaare Zedek Medical CenterShizuoka Cancer CenterSidney Kimmel Comprehensive Cancer Center at Jefferson HealthTaipei Veterans General HospitalTawam HospitalTel Aviv Sourasky Medical CenterThe Ottawa Hospital Cancer Centre / Ottawa Hospital Research InstituteTohoku University HospitalTUM Klinikum rechts der Isar / CCC MünchenUMC Utrecht Cancer CenterUNICANCERUniversity Cancer Center Mainz (UCT Mainz) / Universitätsmedizin MainzUniversity Hospitals Birmingham / University of Birmingham Cancer Research CentreUniversity of Arizona Cancer CenterUniversity of Malaya Medical CentreUniversity of Wisconsin Carbone Cancer CenterUppsala University Hospital / Uppsala UniversityUSC Norris Comprehensive Cancer CenterUZ Leuven / Leuven Cancer InstituteVanderbilt-Ingram Cancer CenterVelindre Cancer CentreWalter and Eliza Hall Institute of Medical ResearchWeizmann Institute of ScienceWellcome Sanger InstituteWest Japan Oncology GroupZhongshan Hospital, Fudan University

pathways

7
Field cancerisationMicrobiome–tumour interactionsPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)VEGF angiogenesisWnt / β-catenin

terms

19
AdenocarcinomaAdolescent and young adult (AYA) oncologyAlcohol-attributable cancerCirculating tumour DNA (ctDNA)Clinical complete response (cCR)Consensus molecular subtypes (CMS1-4)Faecal immunochemical test (FIT)Glycaemic index and glycaemic loadLGR5Lynch syndromeMetabolic syndrome and insulin resistanceMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Minimal / molecular residual disease (MRD)Neoadjuvant / adjuvant / perioperativeObesity-related cancers (IARC list of 13)Peritoneal metastasisSidedness (left vs right colon)Tumour markerTumour-agnostic (tissue-agnostic) approval

trials

20
Add-AspirinALASCCAATOMIC (Alliance A021502)AZUR-1BREAKWATERCHALLENGE (CCTG CO.21)CheckMate 8HWCIRCULATE-Japan (GALAXY / VEGA / ALTAIR)CodeBreaK 300CRYSTAL & FIRE-3DESTINY-CRC02DYNAMICFRESCO-2KEYNOTE-177MOUNTAINEER & MOUNTAINEER-03NICHE-2PARADIGMPonsegromab phase 2 in cancer cachexiaPREHAB: multimodal prehabilitation before colorectal cancer surgerySUNLIGHT

pairings

5
Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRCBRAF inhibitor + MEK inhibitorctDNA MRD → adjuvant therapy decisionKRAS G12C inhibitor + anti-EGFR antibody (colorectal)Neoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancer

roadmaps

1
KRAS roadmap: undruggable → G12C → pan-RAS

ideas

80
A biomarker-directed trial of vitamin D after surgery for digestive tract cancersA blood test for the pre-metastatic nicheA cheap old tablet to restore appetiteA dietitian in every gastrointestinal and head and neck tumour boardA dose-finding trial for exercise after cancerA frameshift neoantigen vaccine for Lynch syndrome carriers as the first preventive cancer vaccine approvalA funded programme of organ-preservation trials to avoid radical surgeryA national residual-disease weather service: serial blood tests for every curatively treated patient, pooledA prevention programme for chemotherapy nerve damage: SARM1 inhibitors, cooling and compressionA public fund and label pathway to trial generic drugs against cancerA randomised trial of a shared-antigen vaccine to prevent Lynch syndrome cancersA ring-fenced metastasis programme with metastasis-specific endpointsA test to tell true oligometastatic disease from hidden widespread spreadA trial of GLP-1 weight-loss drugs with cancer as the primary outcomeA video-based surgical quality registry linking assessed skill to cancer outcomesAutomated combination discovery: patient-sample screens feeding Bayesian platform trialsAutomatic germline testing for every cancer type where it changes careBank three spatially separate tumour blocks from every resectionBorrow from past control arms to shrink the control group in phase 3Break the neutrophil DNA nets that catch tumour cells after surgeryCancer interception vaccines for high-risk carriersCancer warnings on alcohol labels, evaluated as a natural experimentCheap perioperative beta-blocker plus anti-inflammatory to blunt surgical stressCombine the new anti-wasting antibody with exercise and proteinConfirm or refute the harm of antioxidant supplements during chemotherapyControlled feeding trials to separate ultra-processing from caloriesCovalent chemistry for the RAS mutations that still have no drugctDNA-guided adjuvant therapy as the default in stage II-III colon cancerDose chemotherapy by muscle mass, not body surface areaEngineered bacteria that live in tumours and manufacture drugs thereEvaluate alcohol minimum unit pricing against cancer incidenceFactorial trials that test several cheap generics at once in the adjuvant settingFour weeks of training and nutrition before major cancer surgery, as standardGet biomarker-directed aspirin after colorectal surgery into labels and guidelinesGet every Lynch syndrome carrier onto the right dose of aspirinGrow each trial patient's tumour as organoids to decide which platform arm opens nextKeep a freshly removed tumour alive on a pump and test drugs in itLink bariatric and GLP-1 registries to cancer registries in every country that has bothLook for the resistant sub-population before the first doseMake every cold tumour hot: a coordinated programme to reprogramme immune-excluded tumoursMaking microsatellite-stable colorectal cancer immunotherapy-responsiveMandatory staged registries for new surgical techniques before wide adoptionMatch therapy to the type of scar-forming cell in the tumourMechanically pulverise one tumour with ultrasound to wake the immune systemMetastasis prevention as a formal indication with its own trials and regulatory pathwayMultimodal prehabilitation for older patients before major cancer surgeryOff-the-shelf KRAS vaccines after pancreatic cancer surgeryOff-the-shelf natural killer cells to sweep up residual diseaseOffer the blood test for bowel cancer only to people who refuse stool tests or colonoscopyOncology teams order germline tests; tele-genetic counsellors handle the resultsPatent-free open-source development of repurposed and off-patent cancer drugsPathologists order genomic profiling automatically at diagnosis of advanced cancerPay for supervised exercise the way we pay for drugsPerioperative beta-blocker plus COX-2 inhibitor to reduce metastasis after surgeryPersonalised stool-test cut-offs by age, sex and prior resultsPersonalised vaccines given only when the blood test turns positivePopulation germline screening for hereditary cancer genes with cascade testingPre-consented cohorts that can be randomised to future trials (TwiCs)Reprogramme suppressive macrophages instead of trying to delete themReprogramme the liver's own immune cells to refuse metastasesRisk-stratified follow-up: low-risk survivors to primary care with fast re-entrySexual health assessed and treated as a standard toxicity domainSMART designs to test treatment strategies, not just single drugsSocial impact bonds for cancer prevention, repaid from avoided treatment costsStanding reflex biomarker panels per tumour type, run without an oncologist's orderStrip the platelet coat off travelling tumour cells in ctDNA-positive patientsStructured exercise prescribed like a drug in all curative-intent cancer careStructured mentorship so district general surgeons perform common cancer operations safelyTest DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhereTrain the bone marrow to make better anti-tumour immune cellsTreat insomnia in survivors and measure whether the cancer noticesTwo-week pre-operative windows to compare combination biology head to headUnmask hidden antigens with a short epigenetic course before immunotherapyUpfront reduced-dose regimens tested head-to-head in frail older patientsUse a polygenic risk score to set when screening startsUse pre-surgery immunotherapy windows as the field's biomarker engineUse tumour DNA in blood to decide when to pause treatment in metastatic cancerWhen the blood test is positive, hunt for the lesion with sensitive imagingWRN inhibitors: a second synthetic-lethal win for mismatch-repair cancersZebrafish avatars for a drug answer within a week

collections

1
Colorectal Cancer Alliance

people

41
Alan P. VenookAndrea CercekAndrés CervantesBert VogelsteinCarsten BokemeyerChadwick BosemanCharles D. BlankeDame Deborah JamesDavid CunninghamDongsheng TuDung T. LeElena ÉlezEric R. FearonFeng WangFrank McCormickHagen F. KenneckeHermann BrennerJaime FeliuJin LiJosep TaberneroKatie CouricKenneth W. KinzlerKevan M. ShokatLuis A. Diaz Jr.Matthew MeyersonMyriam ChalabiPaulo HoffPeter J. O'DwyerRené BernardsRui-Hua XuRyan B. CorcoranSang Joon ShinSemir BeyazStephen SuttonSteven A. RosenbergTae Won KimTae-You KimTakayuki YoshinoTanios Bekaii-SaabVincenzo ValentiniVolker Heinemann

bottlenecks

15
AI that is built but not validated or deployedCold tumours and the immunosuppressive microenvironmentDormant cells and minimal residual diseaseFragmented care and guideline gapsInherited risk is mostly unidentifiedKnowledge reaches practice too slowlyMetastasis is understood least and studied lastMisinformation and unproven therapiesMost lethal cancers are found lateNo incentive to repurpose cheap drugsNo one can predict who responds to immunotherapyOlder and multimorbid patients are excluded and undertreatedPreclinical models that do not predict peoplePrevention we already have is not deployedThe undruggable drivers

key papers

19
Alcohol caused an estimated 741,000 cancers worldwide in 2020BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancerCAPP2: two years of aspirin cuts bowel cancer in Lynch syndrome by more than a third over 10 yearsCercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiencyCHALLENGE: a structured exercise programme after chemotherapy improves survival in colon cancerCodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancerDostarlimab alone cures mismatch-repair-deficient rectal cancer without surgery or radiotherapyDYNAMIC: a blood test safely halved chemotherapy use after surgery for stage II colon cancerFirst trial of a vaccine against the shared neoantigens of mismatch-repair-deficient cancersGALAXY: tumour DNA in blood four weeks after bowel cancer surgery predicts relapse tenfoldIARC verdict: excess body fat causes 13 cancersKEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancerLe 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organLe 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approvalMinnesota trial: a yearly stool blood test cuts bowel cancer deaths by a thirdNICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patientsNICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patientsNordICC: inviting people to a screening colonoscopy reduced bowel cancer, but less than expectedOstrem and Shokat: the hidden pocket that made KRAS G12C druggable