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Screening more than a thousand lung cancers found a rearranged ROS1 gene in about one in sixty, in younger patients who had mostly never smoked, and the first patient treated with a matched pill nearly cleared her cancer.
A fluorescence in situ hybridisation assay was used to screen 1,073 patients with non-small-cell lung cancer, and rearrangement status was correlated with clinical characteristics, overall survival and ALK status. Eighteen tumours, 1.7%, were ROS1-rearranged and 31, 2.9%, were ALK-rearranged. Compared with the ROS1-negative group, ROS1-rearranged patients were significantly younger and more likely to be never smokers, all tumours were adenocarcinomas with a tendency towards higher grade, and overall survival did not differ. A ROS1-rearranged cell line and cells transfected with CD74-ROS1 were sensitive to crizotinib, and one patient treated in an expanded phase 1 cohort showed tumour shrinkage approaching a complete response.
It defined a class of lung cancer by a rearrangement and a clinical phenotype at the same time, and it is the reason ROS1 testing is recommended for every patient with adenocarcinoma rather than only for those with an obvious risk profile.
Shares Alice T. Shaw, ROS1, Massachusetts General Hospital Cancer Center, Crizotinib.
Shares Alice T. Shaw, Massachusetts General Hospital Cancer Center, Crizotinib, ALK.
Shares Alice T. Shaw, FISH / ISH (in situ hybridisation), Massachusetts General Hospital Cancer Center, Crizotinib.
Shares FISH / ISH (in situ hybridisation), Crizotinib, Gene fusion, Driver mutation.
Shares ROS1 fusion (ROS1-positive), Cytogenetics and FISH, ROS1, FISH / ISH (in situ hybridisation).
Shares Alice T. Shaw, ROS1, Crizotinib, ALK.
Shares ROS1, Crizotinib, Gene fusion, ALK.
Shares Massachusetts General Hospital Cancer Center, Crizotinib, Gene fusion, ALK.