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One of the few mutations in a tumour that actually causes it to grow. Everything else is a passenger along for the ride. Drivers are the mutations drugs are aimed at.
A tumour with thousands of mutations usually has two to eight drivers that confer a growth advantage; the rest are passengers that happened to be present in the cell that became cancerous. Drivers cluster in a few hundred genes: oncogenes activated by mutation or amplification (EGFR, KRAS, BRAF, HER2, ALK) and tumour suppressors lost by mutation or deletion (TP53, RB1, PTEN). Genomic profiling looks for known drivers because a tumour that depends on one can often be treated with a drug against it, the phenomenon called oncogene addiction.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.
Stage III lung cancer is now treated by genotype as well as by stage: an EGFR mutation moves a patient from durvalumab consolidation to osimertinib consolidation. It is also the strongest hazard ratio in the lung cancer literature, which is a reason to read the overall survival data carefully when they arrive.
Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.
It reframes air quality as cancer policy rather than respiratory policy, and it explains the shape of lung cancer in never-smokers: the mutations are common and mostly silent, and what differs is whether something inflames the tissue enough to let one of them grow.
Adding chemotherapy to osimertinib delays progression. Whether it extends life, and whether the same benefit could be had by giving the chemotherapy later to the patients who need it, is what the overall survival analysis and the registry watch on this roadmap are for.
It separates two explanations that are usually run together. Some of the difference in prostate cancer outcomes by race is in the tumour genome and persists when access to the same centre is held constant, and some of it tracks with income rather than with ancestry, so equalising access alone would not eliminate the gap.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
A rare driver with a real drug, and a warning about biomarker thresholds: the same gene, tested the same way, predicts response or does not depending on a copy-number cut-off that has to be measured rather than assumed.
Shares Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer, Differences in prostate cancer genomes by self-reported race, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, Genomic correlates of clinical outcome in advanced prostate cancer.
Shares RHOA G17V, Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies.
Shares Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas, Genomic landscape of lung adenocarcinoma in East Asians, Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Shares Lung adenocarcinoma promotion by air pollutants, Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer, EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer.
Shares CD74-NRG1 fusions in lung adenocarcinoma, ROS1 rearrangements define a unique molecular class of lung cancers, Genomic landscape of lung adenocarcinoma in East Asians, Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies.
Shares Differences in prostate cancer genomes by self-reported race, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, A genetic model for colorectal tumorigenesis, Genetic alterations during colorectal-tumor development.
Shares Differences in prostate cancer genomes by self-reported race, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, SPOP mutation.
Shares Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer, Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression, The long tail of oncogenic drivers in prostate cancer, TMPRSS2-ERG fusion (and the other ETS rearrangements).