TRK inhibitors in cancer therapeutics: Recent advances and future perspectives.

Tropomyosin receptor kinase (TRK), belonging to the tyrosine kinase family, is associated with tumor proliferation, invasion, and survival in various cancers. Upon activation by neurotrophic factors, TRK regulates crucial cellular processes through downstream signaling pathways. Dysregulation of TRK signaling can lead to a range of diseases including cancers. Moreover, mutations in TRK kinases leading to resistance remain a critical issue, necessitating the discovery of new TRK inhibitors to overcome acquired resistance. Recently, several selective TRK inhibitors have been reported, making it possible to address off-target effects and adverse reactions associated with the target. This review summarizes the recent advances in small molecular TRK inhibitors with diverse structural types, activities, and selectivity. It highlights promising small molecules that have shown breakthrough achievements in the field.