Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
Department of Chemistry and Pharmacy, Molecular and Clinical Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
Cells. 2020 Nov 25;9(12):2540. doi: 10.3390/cells9122540.
Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death and is the most common type of liver cancer. Due to the current paucity of drugs for HCC therapy there is a pressing need to develop new therapeutic concepts. In recent years, the role of Serum Response Factor (SRF) and its coactivators, Myocardin-Related Transcription Factors A and B (MRTF-A and -B), in HCC formation and progression has received considerable attention. Targeting MRTFs results in HCC growth arrest provoked by oncogene-induced senescence. The induction of senescence acts as a tumor-suppressive mechanism and therefore gains consideration for pharmacological interventions in cancer therapy. In this article, we describe the key features and the functional role of senescence in light of the development of novel drug targets for HCC therapy with a focus on MRTFs.
肝细胞癌 (HCC) 已成为癌症相关死亡的主要原因，也是最常见的肝癌类型。由于目前 HCC 治疗药物的匮乏，因此迫切需要开发新的治疗理念。近年来，血清反应因子 (SRF) 及其共激活因子肌球蛋白相关转录因子 A 和 B (MRTF-A 和 -B) 在 HCC 形成和进展中的作用受到了广泛关注。靶向 MRTFs 可导致 HCC 生长停滞，这是由癌基因诱导的衰老引起的。衰老的诱导作为一种肿瘤抑制机制，因此在癌症治疗的药理学干预中得到了考虑。在本文中，我们将根据 HCC 治疗新药物靶点的发展，描述衰老的关键特征和功能作用，重点介绍 MRTFs。
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