# Tropomyosin 3 Gene Fusions in Cancers: From Mechanisms to Treatments—A Comprehensive Review

## TL;DR

This review explores how TPM3 gene fusions contribute to cancer development and treatment, focusing on their mechanisms and therapeutic implications.

## Contribution

The paper provides a comprehensive overview of TPM3 gene fusions in cancer, highlighting their role and therapeutic relevance.

## Key findings

- TPM3 gene fusions like TPM3—NTRK1, TPM3—ALK, and TPM3—ROS1 drive oncogenesis by activating tyrosine kinases.
- Tyrosine kinase inhibitors targeting these fusions show therapeutic promise but face challenges like resistance and tumor heterogeneity.
- TPM3 fusions are found in multiple cancer types, emphasizing their clinical significance in precision oncology.

## Abstract

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.

This review elucidates the molecular mechanisms underpinning TPM3 gene fusions, delineates the tumor types associated with these fusions, and examines their clinical implications.

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.

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.