Yousafzai Neelum Aziz, Jin Hongchuan, Ullah Mujib, Wang Xian
Department of Medical Oncology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University Hangzhou 310020, Zhejiang, China.
Department of Medical and Health Sciences, University of Poonch Rawalakot AJK 12350, Pakistan.
Am J Cancer Res. 2021 Nov 15;11(11):5233-5248. eCollection 2021.
Cancer is a big group of diseases and one of the leading causes of mortality worldwide. Despite enormous studies and efforts are being carried out in understanding the cancer and developing drugs against tumorigenesis, drug resistance is the main obstacle in cancer treatments. Chemotherapeutic treatment is an important part of cancer treatment and drug resistance is getting gradually multidimensional with the advancement of studies in cancer. The underlying mechanisms of drug resistance are largely unknown. Sirtuin1 (SIRT1) is a type of the Class III histone deacetylase family that is distinctively dependent on nicotinamide adenine dinucleotide (NAD+) for catalysis reaction. SIRT1 is a molecule which upon upregulation directly influences tumor progression, metastasis, tumor cell apoptosis, autophagy, DNA repair, as well as other interlinked tumorigenesis mechanism. It is involved in drug metabolism, apoptosis, DNA damage, DNA repair, and autophagy, which are key hallmarks of drug resistance and may contribute to multidrug resistance. Thus, understanding the role of SIRT1 in drug resistance could be important. This study focuses on the SIRT1 based mechanisms that might be a potential underlying approach in the development of cancer drug resistance and could be a potential target for drug development.
癌症是一大类疾病，是全球主要死因之一。尽管在了解癌症和研发抗肿瘤发生的药物方面进行了大量研究并付出了诸多努力，但耐药性仍是癌症治疗的主要障碍。化疗是癌症治疗的重要组成部分，随着癌症研究的进展，耐药性正逐渐呈现多维度特点。耐药性的潜在机制在很大程度上尚不清楚。沉默调节蛋白1（SIRT1）是Ⅲ类组蛋白去乙酰化酶家族的一种，其催化反应独特地依赖烟酰胺腺嘌呤二核苷酸（NAD +）。SIRT1是一种分子，其上调后会直接影响肿瘤进展、转移、肿瘤细胞凋亡、自噬、DNA修复以及其他相互关联的肿瘤发生机制。它参与药物代谢、凋亡、DNA损伤、DNA修复和自噬，这些都是耐药性的关键特征，可能导致多药耐药。因此，了解SIRT1在耐药性中的作用可能很重要。本研究聚焦于基于SIRT1的机制，这些机制可能是癌症耐药性发展的潜在基础途径，并且可能成为药物开发的潜在靶点。
