TRK inhibition in soft tissue sarcomas: A comprehensive review

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Soft-tissue sarcomas (STS) are rare mesenchymal tumors with limited effective treatment options.
• Precision oncology offers potential for targeted therapies in STS.
• Neurotrophic receptor tyrosine kinase (NTRK) gene fusions are oncogenic drivers found across various tumor types, including STS.

Purpose of the Study:

• To review methods for detecting NTRK fusions in STS.
• To discuss the incidence, diagnosis, and management of NTRK fusions in STS.
• To highlight the therapeutic potential of NTRK inhibitors in advanced STS.

Main Methods:

• Literature review of studies on NTRK fusions in STS.
• Analysis of diagnostic techniques for NTRK fusion detection.
• Review of clinical data on NTRK inhibitor efficacy in STS.

Main Results:

• NTRK fusions are rare but significant oncogenic drivers in STS.
• Larotrectinib and entrectinib are approved NTRK inhibitors offering new therapeutic avenues.
• These inhibitors are particularly valuable in advanced STS due to poor prognosis and limited options.

Conclusions:

• NTRK fusions represent actionable targets in STS.
• Accurate detection and targeted inhibition of NTRK fusions can improve outcomes in advanced STS.
• Further research into NTRK fusion-positive STS is warranted.