Abstract
BACKGROUND: Tropomyosin 3 (TPM3), one of the four tropomyosin genes, is predominantly expressed in eukaryotic cells. As a crucial regulatory protein, TPM3 associates with actin within thin myofilaments, thereby playing an essential role in the regulation of muscle contraction. Beyond its fundamental function in muscle physiology, TPM3 is implicated in oncogenesis. OBJECTIVE: This review elucidates the molecular mechanisms underpinning TPM3 gene fusions, delineates the tumor types associated with these fusions, and examines their clinical implications. FINDINGS: Gene fusions such as TPM3-NTRK1, TPM3-ALK, and TPM3-ROS1 have been identified as oncogenic drivers in various cancers. These fusions promote constitutive activation of tyrosine kinases, disrupt normal cellular signaling, and consequently accelerate tumorigenesis. Malignancies harboring TPM3 fusions encompass several tumor categories. With the advent of tyrosine kinase inhibitors (TKIs) targeting NTRK1, ALK, and ROS1 fusions, these rearrangements have gained significant therapeutic relevance. However, resistance mechanisms and tumor heterogeneity pose ongoing challenges to targeted therapy. CONCLUSION: By synthesizing current evidence, this review aims to provide insights into the diagnostic, prognostic, and therapeutic landscape of TPM3-related gene fusions, fostering advancements in precision oncology.