Title

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer

Publication Date

2015

Journal Title

Lancet Oncol

Abstract

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy.

Volume Number

16

Issue Number

13

Pages

e510-21

Document Type

Article

EPub Date

2015/10/05

Status

Faculty

Facility

School of Medicine

Primary Department

Radiation Medicine

PMID

26433824

DOI

10.1016/s1470-2045(15)00013-3