TRK inhibition in soft tissue sarcomas: A comprehensive review

Tarek Assi 1Elie Rassy 2Hussein Nassereddine 2Fadi Farhat 2Fadi El Karak 2Joseph Kattan 2Marwan Ghosn 2

Affiliations

1Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon. Electronic address: tarekassi@gmail.com.

2Hematology-Oncology Department, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon.

PMID: 32201016

DOI: 10.1053/j.seminoncol.2020.02.009

Abstract

Soft-tissue sarcomas (STS) are a group of rare mesenchymal tumors that constitutes ∼1% of all solid tumors. It remains a rare tumor which lacks effective treatment options. Precision oncology may be of interest in this regard by identifying potential targets for emerging novel therapies. Neurotrophic receptor tyrosine kinase (NTRK) fusions are rare oncogenic driver mutations found in a broad range of common and rare tumor subtypes including STS. The recent approvals of NTRK inhibitors (larotrectinib and entrectinib) represent new therapeutic options in the drug armamentarium especially valuable in advanced STS given the paucity of treatment options and the generally poor prognosis of these tumors. We review the methods used to detect NTRK fusions in STS with focus on incidence, diagnosis and management of these rare and intriguing oncogenic targets.

Keywords: Cancer; Entrectinib; Fusion; Larotrectinib; NTRK; Soft tissue sarcomas.

Conflict of interest statement

Declaration of Competing Interest None.