NTRK gene fusions in solid tumors: agnostic relevance, prevalence and diagnostic strategies

Area of Science:

• Oncology
• Molecular Pathology
• Precision Medicine

Background:

• Precision medicine utilizes innovative drugs targeting specific molecular alterations in cancer patients.
• Agnostic treatments offer therapeutic options irrespective of tumor site or type, contingent on target detection.
• Identifying rare molecular targets presents a significant challenge in diagnostic molecular pathology.

Purpose of the Study:

• To review the prevalence of Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusions across various solid tumors.
• To present a comprehensive diagnostic algorithm for NTRK gene fusion detection.
• To propose an innovative pathological workflow for rapid screening of these alterations.

Main Methods:

• Literature review of studies reporting NTRK gene fusion prevalence in solid tumors.
• Analysis of diagnostic strategies and pathological workflows for molecular alteration detection.
• Synthesis of data on tumor site, histotype, and prevalence of NTRK gene fusions.

Main Results:

• NTRK gene fusions occur at high frequency in rare neoplasms and at low frequency in common tumors.
• The review consolidates data on NTRK fusion prevalence from extensive studies.
• A diagnostic algorithm and workflow for NTRK fusion screening are detailed.

Conclusions:

• Knowledge of tumor-specific prevalence aids in identifying NTRK gene fusions within an agnostic treatment framework.
• The proposed diagnostic algorithm and workflow facilitate efficient screening for NTRK alterations.
• Effective detection of rare molecular targets is essential for advancing precision oncology.