American Society of Clinical Oncology
ALK in Lung Cancer: Past, Present, and Future
Alice T. Shaw? and Jeffrey A. Engelman
+ Author Affiliations
Alice T. Shaw and Jeffrey A. Engelman, Massachusetts General Hospital Cancer Center, Boston; Alice T. Shaw, Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA.
Corresponding author: Alice T. Shaw, MD, PhD, Massachusetts General Hospital Cancer Center, Yawkey 7B, 32 Fruit St, Boston, MA 02114; email: ashaw1@partners.org.
Abstract
In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non–small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers