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Expert Opin Investig Drugs. 2015;24(11):1493-500. doi: 10.1517/13543784.2015.1096344. Epub 2015 Oct 12.

Entrectinib: a potent new TRK, ROS1, and ALK inhibitor.

Author information

1
a Phase I - Early Clinical Trials Unit, Oncology Department , Antwerp University Hospital and Center for Oncological Research (CORE), Antwerp University , Edegem , Belgium.
2
b Oncology Department , National Cancer Institute (INEN) , Lima , Peru.
3
c Department Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands.
4
d Department of Oncology , ClĂ­nica Universidad de Navarra , Pamplona , Spain.
5
e Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy.
6
f Thoracic Oncology Program , Memorial Cancer Institute, Memorial Health Care System , Pembroke Pines , FL , USA.

Abstract

INTRODUCTION:

Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC.

AREAS COVERED:

This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-clinical studies and clinical trials of entrectinib, a promising novel agent for the treatment of advanced solid tumors with molecular alterations of Trk-A, B and C, ROS1 or ALK.

EXPERT OPINION:

Among the several experimental drugs under clinical development, entrectinib is emerging as an innovative and promising targeted agent. The encouraging antitumor activity reported in the Phase 1 studies, together with the acceptable toxicity profile, suggest that entrectinib, thanks to its peculiar mechanism of action, could play an important role in the treatment-strategies of multiple TRK-A, B, C, ROS1, and ALK- dependent solid tumors, including NSCLC and colorectal cancer. That being said, further evidence for its clinical use is still needed.

KEYWORDS:

ALK; Entrectinib; NTRK1; NTRK2; NTRK3; ROS1; TrkA; TrkB; TrkC; colorectal cancer; non-small cell lung cancer; precision medicine; salivary gland cancer

PMID:
26457764
DOI:
10.1517/13543784.2015.1096344
[Indexed for MEDLINE]

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