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Expert Opinion on Investigational Drugs 2016

The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer.

Samo registrirani uporabniki lahko prevajajo članke
Prijava / prijava
Povezava se shrani v odložišče
Francesco Passiglia
Rafael Caparica
Elisa Giovannetti
Marco Giallombardo
Angela Listi
Patrizia Diana
Girolamo Cirrincione
Christian Caglevic
Luis E Raez
Antonio Russo

Ključne besede

Povzetek

BACKGROUND

Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation.

METHODS

This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in early phase I studies.

CONCLUSIONS

Among the several NTRK-inhibitors, entrectinib and LOXO-101 are those in more advanced stage of clinical development. Both agents have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring NTRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers. Results from ongoing phase II basket trials are eagerly awaited.

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