Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland.
Invest New Drugs. 2021 Apr;39(2):538-563. doi: 10.1007/s10637-020-01032-y. Epub 2020 Nov 7.
Although cisplatin is one of the most common antineoplastic drug, its successful utilisation in cancer treatment is limited by the drug resistance. Multiple attempts have been made to find potential cisplatin chemosensitisers which would overcome cancer cells resistance thus improving antineoplastic efficacy. Autophagy modulation has become an important area of interest regarding the aforementioned topic. Autophagy is a highly conservative cellular self-digestive process implicated in response to multiple environmental stressors. The high basal level of autophagy is a common phenomenon in cisplatin-resistant cancer cells which is thought to grant survival benefit. However current evidence supports the role of autophagy in either promoting or limiting carcinogenesis depending on the context. This encourages the search of substances modulating the process to alleviate cisplatin resistance. Such a strategy encompasses not only simple autophagy inhibition but also harnessing the process to induce autophagy-dependent cell death. In this paper, we briefly describe the mechanism of cisplatin resistance with a special emphasis on autophagy and we give an extensive literature review of potential substances with cisplatin chemosensitising properties related to autophagy modulation.
虽然顺铂是最常用的抗肿瘤药物之一,但由于耐药性,其在癌症治疗中的成功应用受到限制。人们已经多次尝试寻找潜在的顺铂化疗增敏剂,以克服癌细胞的耐药性,从而提高抗肿瘤疗效。自噬调节已成为与上述主题相关的一个重要研究领域。自噬是一种高度保守的细胞自噬过程,参与对多种环境应激源的反应。在顺铂耐药的癌细胞中,自噬的基础水平很高,这被认为赋予了生存优势。然而,目前的证据支持自噬在促进或限制癌变方面的作用,具体取决于具体情况。这鼓励人们寻找调节该过程的物质来减轻顺铂耐药性。这种策略不仅包括简单的自噬抑制,还包括利用该过程诱导自噬依赖性细胞死亡。本文简要描述了顺铂耐药的机制,特别强调了自噬,并对与自噬调节相关的具有顺铂化疗增敏特性的潜在物质进行了广泛的文献综述。