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When a cancer depends so completely on one mutated gene that blocking it collapses the tumour.
Oncogene addiction is the state in which a cancer depends so completely on a single mutated gene that blocking it collapses the tumour. The term was coined by Weinstein in 2002, and EGFR, ALK, BCR-ABL, KIT and BRAF V600E tumours exemplify it: dramatic responses to a single agent, followed by acquired resistance. It underlies the whole targeted-therapy paradigm and so is linked to the Small-molecule kinase inhibitors technology and the hallmark of sustaining proliferative signalling. Readers meet it in the Chronic myeloid leukaemia (CML) and Gastrointestinal stromal tumour (GIST) entries, the Gefitinib and Crizotinib drug records, the FLAURA and ADAURA papers, the entries for Brian Druker and Bud Romine, and ideas on molecular glues against MYC-MAX.
Showing the technology this term belongs to: Small-molecule kinase inhibitors.
Young adults with a grade 2 IDH-mutant glioma who have had surgery can now take a daily tablet that slows or reverses tumour growth and defers radiotherapy and chemotherapy, both of which carry long-term cognitive costs, by years. It confirms that the IDH mutation is a driver that can be targeted, not just a marker. Whether it improves survival or cognition over the long term, and whether it helps in higher-grade or previously treated tumours, is unknown.
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.
Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.
The current first choice for ALK-positive lung cancer in most guidelines, and the strongest evidence in solid tumour oncology that a drug can be designed to work inside the brain. Five-year follow-up has since shown the majority of patients still progression-free.
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.
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.
The trial that made ALK testing worth doing. It is also the clearest case in oncology of a drug finding its disease after the fact: crizotinib entered the clinic as a MET inhibitor and became an ALK drug because somebody checked.
The trial that turned EGFR testing into a standard of care rather than a research assay, and the clearest demonstration in oncology that a clinically selected population can hide two opposite treatment effects inside one positive result.
Shares PROFILE 1001 ROS1 expansion cohort, University of Colorado Cancer Center, PROFILE 1014, Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Shares Oncogene, University of Colorado Cancer Center, Hallmark: sustaining proliferative signalling, Guangdong Provincial People's Hospital.
Shares PROFILE 1001 ROS1 expansion cohort, University of Colorado Cancer Center, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer, NTRK fusion-positive non-small-cell lung cancer.
Shares Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer, Crizotinib, ALK-positive non-small-cell lung cancer.
Shares PROFILE 1001 ROS1 expansion cohort, NTRK fusion-positive non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer, ALK-positive non-small-cell lung cancer.
Shares PROFILE 1014, Tyrosine kinase inhibitor (TKI), Crizotinib, ALK-positive non-small-cell lung cancer.
Shares PROFILE 1014, Tyrosine kinase inhibitor (TKI), Crizotinib, ALK-positive non-small-cell lung cancer.
Shares Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib, Gefitinib, Driver mutation, Receptor tyrosine kinase activation.