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RESEARCH PRODUCT
Entrectinib: a potent new TRK, ROS1, and ALK inhibitor
Elisa GiovannettiMarco GiallombardoRossana RuizFrancesco PassigliaMarc PeetersChristian RolfoLuis E. RaezIgnacio Gil-bazoAntonio Russosubject
Receptor Protein-Tyrosine KinasesEntrectinibNTRK1NTRK2NTRK3Receptor tyrosine kinaseEntrectinibMalignant transformationAntineoplastic AgentNeoplasmsProtein-Tyrosine KinaseALK; colorectal cancer; Entrectinib; non-small cell lung cancer; NTRK1; NTRK2; NTRK3; precision medicine; ROS1; salivary gland cancer; TrkA; TrkB; TrkC; Animals; Antineoplastic Agents; Benzamides; Humans; Indazoles; Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Receptor; trkA; Receptor; trkB; Receptor; trkC; Pharmacology; Pharmacology (medical)Anaplastic Lymphoma KinasePharmacology (medical)salivary gland cancerProto-Oncogene ProteinbiologyTrkAPharmacology. TherapyTrkCTrkBGeneral MedicineProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinaseBenzamidesmedicine.symptomROS1ReceptorHumanIndazolesmedicine.drug_classprecision medicineAntineoplastic Agentscolorectal cancerBenzamideProto-Oncogene ProteinsmedicineROS1AnimalsHumansReceptor trkBReceptor trkCReceptor trkAnon-small cell lung cancerPharmacologyAnimalReceptor Protein-Tyrosine KinasesALK inhibitorIndazoleMechanism of actionALKTrk receptorbiology.proteinCancer researchNeoplasmALK; colorectal cancer; Entrectinib; non-small cell lung cancer; NTRK1; NTRK2; NTRK3; precision medicine; ROS1; salivary gland cancer; TrkA; TrkB; TrkC; Animals; Antineoplastic Agents; Benzamides; Humans; Indazoles; Neoplasms; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Receptor trkA; Receptor trkB; Receptor trkC; Pharmacology; Pharmacology (medical)description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 | Expert Opinion on Investigational Drugs |