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转化生长因子β与肺泡横纹肌肉瘤：肿瘤分化与化疗反应的挑战。

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

机构信息

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.

出版信息

Int J Mol Sci. 2024 Feb 28;25(5):2791. doi: 10.3390/ijms25052791.

DOI:10.3390/ijms25052791
PMID:38474036
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10932473/
Abstract

Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, or . 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.

摘要

肺泡横纹肌肉瘤 (ARMS) 是横纹肌肉瘤 (RMS) 的侵袭性亚型，与染色体易位事件相关，导致两种致癌融合基因中的一种， 或. ARMS 患者表现出多效细胞因子转化生长因子 β (TGF-β) 的过度表达。TGF-β1 的这种过表达导致下游转录因子 SNAIL 的表达增加，促进上皮细胞向间充质转化 (EMT)。TGF-β 的过度表达也抑制成肌分化，使 ARMS 患者对化疗高度耐药。在这篇综述中，我们首先描述了不同类型的 RMS，然后重点介绍了 ARMS 以及 TGF-β 在这种肿瘤类型中的作用。接下来，我们强调了当前的化疗策略，包括美国食品和药物管理局批准的药物长春新碱、放线菌素 D 和环磷酰胺 (VAC) 的组合；卡博替尼；硼替佐米；长春瑞滨；AZD 1775；和顺铂。最后，我们讨论了靶向 ARMS 肿瘤细胞分化的化疗药物，包括全反式视黄酸 (ATRA) 和 5-氮杂胞苷。深入了解 TGF-β1 等信号通路在 ARMS 肿瘤细胞分化中的作用，将有助于为未来更有针对性的药物管理提供信息。

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