# Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response

## TL;DR

This paper reviews how TGF-β overexpression in alveolar rhabdomyosarcoma affects tumor differentiation and chemotherapy resistance.

## Contribution

The paper provides a focused review on TGF-β's role in ARMS and explores chemotherapy agents targeting tumor differentiation.

## Key findings

- TGF-β overexpression in ARMS promotes EMT and inhibits myogenic differentiation.
- Current chemotherapy strategies include FDA-approved drugs like VAC and others like cabozantinib and bortezomib.
- Agents like ATRA and 5-Azacytidine are being explored to target tumor cell differentiation in ARMS.

## Abstract

Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.