Bounty of Novel Drugs Ushers In New Era for ALK-Positive NSCLC

Jane de Lartigue, PhD
Published: Tuesday, Feb 13, 2018
lung cancer
During the past decade, ALK inhibitors have followed a rapid trajectory from bench to bedside, taking over from chemotherapy as standard frontline treatment for patients with advanced non– small-cell lung cancer (NSCLC) with ALK gene rearrangements.

-positive NSCLC into a chronic disease.

Adopting Orphan ALK

As its name suggests, the anaplastic lymphoma kinase is a receptor tyrosine kinase that was first identified through its aberrant expression in anaplastic large cell lymphoma.1

 

Figure. ALK Signaling Pathways in Lung Cancer2

ALK Signaling
Beyond this, little is known about the precise biological function of the ALK protein and, until recently, it was considered an “orphan” receptor, with no known activating ligand. Studies have established the augmentor α and β proteins (also known as FAM150B and A, respectively) as the ligands for ALK. Other research suggested that heparin may act as an ALK ligand, but this has not been confirmed in subsequent work, although it may bind to FAM150A and regulate ALK activation in that manner.3

A Lung Cancer Driver

In 2007, a chromosomal rearrangement involving the ALK gene, which resulted in the expression of a dysfunctional fusion protein, was identified in a resected tumor specimen from a 62-year old patient with lung cancer.4

Bench to Bedside

National Comprehensive Cancer Network (NCCN) and International Association for the Study of Lung Cancer guidelines recommend testing all patients who present with advanced NSCLC for ALK fusions because clinical trials have demonstrated the sensitivity of ALK-positive cancers to ALK inhibition.9,10
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Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
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