Comprehensive genomic profiling

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.

Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.

Cancers are defined as much by the tissue they come from as by the mutations they carry, which is why the same drug can work in one organ and fail in another with the same mutation. TCGA is the shared public dataset behind most modern biomarkers and target discovery.

There are not thousands of cancer genes, and any one patient's tumour is driven by only a few of them. That makes targeted sequencing panels sensible, but because most drivers are lost tumour suppressors, drugs exist for only a minority, which is why the same group turned to early detection.