Oncogene addiction in non-small cell lung cancer: Focus on ROS1 inhibition. (April 2017)

• Record Type: Journal Article
• Authors: Facchinetti, Francesco; Rossi, Giulio; Bria, Emilio; Soria, Jean-Charles; Besse, Benjamin; Minari, Roberta; Friboulet, Luc; Tiseo, Marcello
• Is Part Of: Cancer treatment reviews. Volume 55(2017)
• Page Start: 83
• Page End: 95
• Publication Date: 2017-04
• Subjects: Non-small cell lung cancer -- ROS1 rearrangement -- ALK gene fusion -- Crizotinib -- Resistance -- Novel-generation inhibitors; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2017.02.010
• Languages: English
• ISSNs: 0305-7372

Abstract

Highlights: 1–2% of lung adenocarcinomas harbor a ROS1 rearrangement. Detection of ROS1 positivity is suggested in the molecular screening of advanced NSCLC. ALK- and ROS1-rearranged lung cancers share relevant similarities. Crizotinib is significantly active in ROS1-driven diseases. Resistance to crizotinib in ROS1-positive cancers can be overcome by novel inhibitors. Abstract: Detection of molecular aberrations driving the biology and the clinical behavior of advanced non-small cell lung cancer (NSCLC) allows the adoption of specific therapeutic strategies dramatically impacting disease courses. Among these, ROS1 rearrangements are present in 1–2% of lung adenocarcinomas. Thanks to similarities between ALK and ROS1 oncogenes, lessons inferred from ALK can be applied to ROS1-positive NSCLC; nevertheless, disparities exist between diseases mastered by these two fusion genes. In the absence of more common genetic alterations detected in NSCLC (e.g. EGFR and KRAS mutations, ALK gene fusions), seeking for ROS1 rearrangements is crucial. Dedicated molecular diagnostics should be standardized, hopefully relying upon practical and efficient algorithms, comprehending immunohistochemistry and fluorescence in situ hybridisation. The major clinical impact exerted by crizotinib represents the main reason for which not even a sole ROS1-positive tumor should be undetected. The recent approval of the inhibitor by both American and European health agencies would hopefully boost the widespread testing for ROS1, eventually increasing the absolute number of positive cases, potential further source of information regarding molecular and clinical resistance. In vitro and clinical evidence have already been generated concerning crizotinib resistance and strategies to maintain patients under specific driver-inhibition are being successfully developed. Gathering data concerning diagnostics, preclinical evidence, clinical practice and ongoing studies, the present review depicts the current scenario of ROS1 inhibition in NSCLC.