Look for the resistant sub-population before the first dose
Resistance mutations often exist in a tiny fraction of cells before treatment starts. A very sensitive test at diagnosis could find them and prompt a combination from day one.
Duplex or error-corrected sequencing detects variants below 0.01 percent allele fraction. Pre-existing resistance clones (EGFR T790M before first-generation TKIs, KRAS in colorectal cancer before anti-EGFR, ESR1 in breast cancer) predict early failure. The proposal is a baseline ultra-deep panel of known resistance alleles for every patient starting a targeted drug, with a pre-specified rule to add the mechanism-matched second agent if a clone is found.
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
Pages like this
not linked directly; found by shared links- IdeaRe-test the metastasis, not the old primary, before every change of treatment
Shares Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, Comprehensive genomic profiling, Liquid biopsy (ctDNA).
- IdeactDNA-guided dose holidays for lung cancer targeted therapy
Shares Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, EGFR, Liquid biopsy (ctDNA).
- IdeaA clone report from blood at every treatment cycle
Shares Variant allele frequency (VAF), Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, Liquid biopsy (ctDNA).
- InstitutionAichi Cancer Center
Shares EGFR, Comprehensive genomic profiling, HR-positive / HER2-negative breast cancer, Colorectal cancer.
- InstitutionBeatson West of Scotland Cancer Centre / CRUK Scotland Institute
Shares Estrogen receptor (ERα), KRAS, Comprehensive genomic profiling, HR-positive / HER2-negative breast cancer.
- IdeaPause a failed drug so the tumour becomes sensitive to it again
Shares Tumour heterogeneity and clonal evolution, Acquired resistance to every therapy, Liquid biopsy (ctDNA), Non-small-cell lung cancer.
- InstitutionTohoku University Hospital
Shares Estrogen receptor (ERα), HR-positive / HER2-negative breast cancer, Colorectal cancer, Non-small-cell lung cancer.
- InstitutionHealthCare Global Enterprises
Shares Comprehensive genomic profiling, Liquid biopsy (ctDNA), HR-positive / HER2-negative breast cancer, Non-small-cell lung cancer.