Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, India.
Homi Bhaba National Institute, Mumbai, India.
Mol Cell Biol. 2022 Jan 20;42(1):e0048321. doi: 10.1128/MCB.00483-21. Epub 2021 Nov 8.
From initiation through progression, cancer cells are subjected to a magnitude of endogenous and exogenous stresses, which aid in their neoplastic transformation. Exposure to these classes of stress induces imbalance in cellular homeostasis and, in response, cancer cells employ informative adaptive mechanisms to rebalance biochemical processes that facilitate survival and maintain their existence. Different kinds of stress stimuli trigger epigenetic alterations in cancer cells, which leads to changes in their transcriptome and metabolome, ultimately resulting in suppression of growth inhibition or induction of apoptosis. Whether cancer cells show a protective response to stress or succumb to cell death depends on the type of stress and duration of exposure. A thorough understanding of epigenetic and molecular architecture of cancer cell stress response pathways can unveil a plethora of information required to develop novel anticancer therapeutics. The present view highlights current knowledge about alterations in epigenome and transcriptome of cancer cells as a consequence of exposure to different physicochemical stressful stimuli such as reactive oxygen species (ROS), hypoxia, radiation, hyperthermia, genotoxic agents, and nutrient deprivation. Currently, an anticancer treatment scenario involving the imposition of stress to target cancer cells is gaining traction to augment or even replace conventional therapeutic regimens. Therefore, a comprehensive understanding of stress response pathways is crucial for devising and implementing novel therapeutic strategies.
从启动到进展，癌细胞受到大量内源性和外源性应激的影响，这有助于它们的肿瘤转化。暴露于这些应激类别会导致细胞内稳态失衡，作为回应，癌细胞采用信息适应性机制来重新平衡有助于生存和维持生存的生化过程。不同类型的应激刺激会在癌细胞中引发表观遗传改变，导致其转录组和代谢组发生变化，最终导致生长抑制的抑制或凋亡的诱导。癌细胞是对压力表现出保护反应还是屈服于细胞死亡，取决于压力的类型和暴露的持续时间。深入了解癌细胞应激反应途径的表观遗传和分子结构，可以揭示开发新型抗癌治疗方法所需的大量信息。目前的观点强调了由于暴露于不同的物理化学应激刺激（如活性氧 (ROS)、缺氧、辐射、高温、遗传毒性物质和营养剥夺）而导致癌细胞表观基因组和转录组发生改变的现有知识。目前，一种涉及对靶癌细胞施加应激以增强甚至替代传统治疗方案的抗癌治疗方案正在引起关注。因此，全面了解应激反应途径对于设计和实施新的治疗策略至关重要。
