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A small inversion on chromosome 2 fuses two genes and makes a kinase that drives lung cancer. Soda and Mano found it in 5 of 75 tumours, and a drug for it was approved four years later.
Soda, Choi, Enomoto and colleagues, with Mano as senior author, showed that a small inversion within chromosome 2p fuses portions of EML4 and ALK in non-small-cell lung cancer cells, that mouse 3T3 fibroblasts forced to express the fusion form transformed foci and subcutaneous tumours, and that the transcript is present in a subset of patients distinct from those with EGFR mutations.
The four years from this paper to crizotinib's approval in 2011 is the shortest interval from the discovery of a driver to an approved drug in solid tumour oncology, and it happened because crizotinib already existed as a MET inhibitor with incidental ALK activity. That accident is the argument for screening existing compound libraries against every new driver.
The second driver in lung cancer, and the one that proved the first was not a special case. It also established mutual exclusivity as a working assumption: a tumour usually has one driver, so finding it tells you what to give.
One of the most cited trial reports Europe PMC returns for ALK in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
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.
Shares Oncogene addiction, Adenocarcinoma of the lung, Driver mutation, Next-generation sequencing (NGS) and the tag lung-evidence.
Shares Oncogene addiction, Adenocarcinoma of the lung, Driver mutation, Next-generation sequencing (NGS) and the tag lung-evidence.
Shares Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, Crizotinib, Driver mutation, ALK-positive non-small-cell lung cancer and the tag lung-evidence.
Shares Oncogene addiction, Adenocarcinoma of the lung, Driver mutation, Next-generation sequencing (NGS) and the tag lung-evidence.
Shares Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer, Crizotinib, ALK-positive non-small-cell lung cancer, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Nature, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch and the tag lung-evidence.
Shares Driver mutation, Next-generation sequencing (NGS), Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, Receptor tyrosine kinase activation and the tag lung-evidence.
Shares Adenocarcinoma of the lung, Driver mutation, Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch, EGFR and the tag lung-evidence.