Research Progress on Small Molecules Inhibitors Targeting TRK Kinases

Area of Science:

• Oncology
• Molecular Biology
• Drug Discovery

Background:

• Trk gene fusions are key drivers in various cancers, including secretory breast cancer and infantile congenital sarcoma.
• The advent of first-generation TRK inhibitors (Larotrectinib, Entrectinib) marked a milestone, but drug resistance remains a challenge.

Purpose of the Study:

• To review the research progress of first-generation TRK inhibitors.
• To highlight the development of second-generation TRK inhibitors designed to overcome drug resistance.

Main Methods:

• Literature search of relevant and cutting-edge documents.
• Filtering, selection, analysis, and classification of appropriate articles.
• Synthesis of information to address specific research topics.

Main Results:

• Description of Trk protein fusions and their oncogenic role.
• Explanation of Trk kinase composition and signaling pathways.
• Classification of TRK inhibitors based on their ability to overcome drug resistance.

Conclusions:

• Provides a theoretical reference for developing novel TRK inhibitors.
• Summarizes representative and novel TRK inhibitors that address drug resistance.