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.

Rolfo, C., Ruiz, R., Giovannetti, E., Gil-Bazo, I., Russo, A., Passiglia, F., et al. (2015). Entrectinib: A potent new TRK, ROS1, and ALK inhibitor. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 24(11), 1493-1500 [10.1517/13543784.2015.1096344].

Entrectinib: A potent new TRK, ROS1, and ALK inhibitor

Rolfo, Christian;Russo, Antonio;Passiglia, Francesco;Giallombardo, Marco;
2015

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.
Rolfo, C., Ruiz, R., Giovannetti, E., Gil-Bazo, I., Russo, A., Passiglia, F., et al. (2015). Entrectinib: A potent new TRK, ROS1, and ALK inhibitor. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 24(11), 1493-1500 [10.1517/13543784.2015.1096344].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/250579
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