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睾丸生殖细胞肿瘤耐药的分子机制——临床意义。

Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications.

机构信息

Translational Research Unit, Faculty of Medicine, Comenius University; National Cancer Institute, Bratislava, Slovakia.

Department of Oncology, National Cancer Institute, Bratislava, Slovakia.

出版信息

Curr Cancer Drug Targets. 2018;18(10):967-978. doi: 10.2174/1568009618666180102103959.

Abstract

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors' biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

摘要

睾丸生殖细胞肿瘤 (TGCTs) 是 15-35 岁男性中最常见的恶性肿瘤。由于这些肿瘤的生物学和临床特征,它们可以作为一个合适的系统来研究与顺铂治疗耐药相关的分子机制。本文从临床和分子角度描述了治疗耐药性。顺铂耐药性由多种生物学机制决定,包括癌细胞 DNA 修复能力的调节、凋亡细胞死亡途径的改变、基因表达途径的失调、表观遗传改变和 DNA 结合不足。此外,本文还将 TGCTs 描述为一个模型系统,能够研究转移过程中癌症干细胞的细胞特征,并描述可用于研究 TGCTs 治疗耐药性的实验模型。所有上述方面都有助于阐明顺铂耐药性的分子机制,并有助于确定有前途的新治疗靶点。

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