ALK in Non-Small Cell Lung Cancer (NSCLC) Pathobiology, Epidemiology, Detection from Tumor Tissue and Algorithm Diagnosis in a Daily Practice

Abstract

Patients with advanced-stage non-small cell lung carcinoma (NSCLC) harboring an ALK rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. Several increasingly effective ALK inhibitors are now available for treatment of patients. However, despite an initial favorable response to treatment, in most cases relapse or progression occurs due to resistance mechanisms mainly caused by mutations in the tyrosine kinase domain of ALK. The detection of an ALK rearrangement is pivotal and can be done using different methods, which have variable sensitivity and specificity depending, in particular, on the quality and quantity of the patient's sample. This review will first highlight briefly some information regarding the pathobiology of an ALK rearrangement and the epidemiology of patients harboring this genomic alteration. The different methods used to detect an ALK rearrangement as well as their advantages and disadvantages will then be examined and algorithms proposed for detection in daily routine practice.

Keywords: ALK rearrangement, lung cancer, biology, immunohistochemistry, FISH, molecular biology..

Figure 1

Current algorithm proposed at the LPCE (Nice Hospital, France) for ALK testing [incorporating into the standard of care ROS1 status and Epidermal Growth Factor Receptor gene (EGFR) mutation testing in lung adenocarcinoma].