Current Knowledge about Mechanisms of Drug Resistance against ALK Inhibitors in Non-Small Cell Lung Cancer

摘要

Lung cancer is a devastating disease, with non-small cell lung cancer (NSCLC) being the most common subtype. With the development of novel targeted therapeutics, survival times have continuously improved over the past two decades. In a subset of NSCLC, gene rearrangements of the anaplastic lymphoma kinase (ALK), or gene fusions involving ALK, can be determined. ALK-inhibitors are increasingly used as a standard of care in patients with ALK gene abnormalities, and can also be administered as first-line treatment in advanced-stage NSCLC. However, over the disease course, cancers tend to develop resistance mechanisms, warranting the switch from first- to second- or third-generation ALK inhibitors. With this literature review, we aim to give a concise overview about these resistance mechanisms, and what kind of sequential treatment may be feasible if therapy failure upon an ALK inhibitor occurs.