Title:ALK-Positive Non-Small Cell Lung Cancer; Potential Combination Drug Treatments
Volume: 21
Issue: 9
Author(s): Shrestha Nensi and John Ashton*
Affiliation:
- Department of Pharmacology & Toxicology, Otago School of Biomedical Sciences, University of Otago, Dunedin,New Zealand
Keywords:
ALK-positive NSCLC, combination treatment, ALK inhibitor, secondary targets, compound resistance, drug combinations.
Abstract: Advances in chromosomally rearranged ALK positive non-small cell lung cancer have
been dramatic in only the last few years. Survival times have improved dramatically due to the introduction
of ever more efficacious ALK inhibitors. These improvements have been due largely to
improvements in blood-brain barrier penetration and the breadth of ligand binding pocket mutations
against which the drugs are effective. However, the advances maybe slow due to the frequency
of cancers with compound resistance mutations are appearing, suggesting the need to develop
multiple ALK inhibitors to target different compound mutations.Another research area that promises
to provide further gains is the use of drug combinations, with an ALK inhibitor combined with a
drug targeting a “second driver” to overcome resistance. In this review, the range of secondary targets
for ALK+ lung cancer and the potential for their clinical success are reviewed.
