title: The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer.
abstract: 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.
authors.affiliation: a Department of Surgical, Oncology and Oral Sciences - Medical Oncology , University of Palermo , Palermo , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passiglia
authors.affiliation: b Faculdade de Medicina da USP , Instituto do Câncer do Estado de São Paulo , São Paulo , Brasil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Caparica
authors.affiliation: c Dept. Medical Oncology , VU University Medical Center, Cancer Center Amsterdam (CCA) , Amsterdam , The Netherlands.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.affiliation: d Phase I-Early Clinical Trials Unit, Oncology Department , Antwerp University Hospital (UZA) and Center for Oncological Research (CORE) Antwerp University , Edegem , Antwerp , Belgium.|e Department of Biopathology and Medical Biotechnology, Biology and Genetics section , University of Palermo , Palermo , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giallombardo
authors.affiliation: a Department of Surgical, Oncology and Oral Sciences - Medical Oncology , University of Palermo , Palermo , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Listi
authors.affiliation: f Biological, Chemical and Pharmaceutical Sciences and Technologies Department , University of Palermo , Palermo , Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.affiliation: f Biological, Chemical and Pharmaceutical Sciences and Technologies Department , University of Palermo , Palermo , Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
authors.affiliation: g Oncology Department , Fundación Arturo Lopez Pérez , Santiago , Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: Caglevic
authors.affiliation: h Thoracic Oncology Program, Memorial Cancer Institute, Memorial Health Care System, Florida International University , Miami , FL , USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.affiliation: a Department of Surgical, Oncology and Oral Sciences - Medical Oncology , University of Palermo , Palermo , Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.affiliation: d Phase I-Early Clinical Trials Unit, Oncology Department , Antwerp University Hospital (UZA) and Center for Oncological Research (CORE) Antwerp University , Edegem , Antwerp , Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
mesh_terms: D000818:Animals; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D020794:Receptor Protein-Tyrosine Kinases
keywords: NTRK-inhibitors; NTRK1/2/3; TrkA/B/C; lung cancer; targeted therapy