Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond.

Abstract:

:Lung cancer is the leading cause of cancer-related mortality in both sexes, accounting for over one quarter of cancer deaths. Non-small-cell lung cancer (NSCLC) comprises 85%-90% of lung cancer diagnoses and despite advances in multimodality therapies, 5-year survival rates remain dismal with a median survival for patients with metastatic disease of 1 year. The positive outcomes of targeted therapies against the kinase domain of epidermal growth factor receptor in NSCLC triggered consistent efforts to identify the so-called driver mutations as other potential targets. Anaplastic large-cell kinase (ALK) gene rearrangements were identified and targeted resulting in promising response rates in early studies. Unfortunately, most of the patients treated with crizotinib, the first-generation ALK inhibitor, progressed within 9 months. Ceritinib is a second-generation ALK inhibitor that has demonstrated activity in crizotinib-resistant patients, becoming a promising treatment option in this population. Furthermore, additional novel ALK inhibitors and agents targeting alternative pathways have been recruited to rechallenge this evasive disease post-crizotinib resistance.

journal_name

Onco Targets Ther

journal_title

OncoTargets and therapy

authors

Kanaan Z,Kloecker GH,Paintal A,Perez CA

doi

10.2147/OTT.S67262

subject

Has Abstract

pub_date

2015-04-20 00:00:00

pages

885-92

issn

1178-6930

pii

ott-8-885

journal_volume

8

pub_type

杂志文章,评审