Bhushan, B.; Iranpour, R.; Eshtiaghi, A.; da Silva Rosa, S.C.; Lindsey, B.W.; Gordon, J.W.; Ghavami, S. Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response. Int. J. Mol. Sci.2024, 25, 2791.
Bhushan, B.; Iranpour, R.; Eshtiaghi, A.; da Silva Rosa, S.C.; Lindsey, B.W.; Gordon, J.W.; Ghavami, S. Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response. Int. J. Mol. Sci. 2024, 25, 2791.
Bhushan, B.; Iranpour, R.; Eshtiaghi, A.; da Silva Rosa, S.C.; Lindsey, B.W.; Gordon, J.W.; Ghavami, S. Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response. Int. J. Mol. Sci.2024, 25, 2791.
Bhushan, B.; Iranpour, R.; Eshtiaghi, A.; da Silva Rosa, S.C.; Lindsey, B.W.; Gordon, J.W.; Ghavami, S. Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response. Int. J. Mol. Sci. 2024, 25, 2791.
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 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.
Keywords
Rhabdomyosarcoma; Combination-therapy; all trans retinoic acid; TGF-beta1
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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