| Autor: |
Bhushan B; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada.; Department of Anatomy and Cell Biology, School of Biomedical Sciences, Faculty of Science, McGill University, Montreal, QC H3A 0C7, Canada., Iranpour R; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., Eshtiaghi A; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., da Silva Rosa SC; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., Lindsey BW; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., Gordon JW; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada., Ghavami S; Department of Human Anatomy and Cell Science, Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0W2, Canada.; Department of Biomedical Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB R3E 0V9, Canada. |
| Abstrakt: |
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. |
