Nanobiotech Lab, Kirori Mal College, University of Delhi, Delhi, 110007, India.
School of Natural Sciences, University of Central Lancashire, PR1 2HE, UK.
Nanomedicine (Lond). 2021 May;16(12):1049-1065. doi: 10.2217/nnm-2020-0443. Epub 2021 May 10.
Apoptotic death evasion is a hallmark of cancer progression. In this context, past decades have witnessed cytotoxic agents targeting apoptosis. However, owing to cellular defects in the apoptotic machinery, tumors develop resistance to apoptosis-based cancer therapies. Hence, targeting nonapoptotic cell-death pathways displays enhanced therapeutic success in apoptosis-defective tumor cells. Exploitation of multifunctional properties of engineered nanoparticles may allow cancer therapeutics to target yet unexplored pathways such as ferroptosis, autophagy and necroptosis. Necroptosis presents a programmed necrotic death initiated by same apoptotic death signals that are caspase independent, whereas autophagy is self-degradative causing vacuolation, and ferroptosis is an iron-dependent form driven by lipid peroxidation. Targeting these tightly regulated nonapoptotic pathways may emerge as a new direction in cancer drug development, diagnostics and novel cancer nanotherapeutics. This review highlights the current challenges along with the advancement in this field of research and finally summarizes the future perspective in terms of their clinical merits.
细胞凋亡逃避是癌症进展的一个标志。在这种情况下，过去几十年见证了针对细胞凋亡的细胞毒性药物。然而，由于细胞凋亡机制中的细胞缺陷，肿瘤对基于细胞凋亡的癌症治疗产生了耐药性。因此，针对非细胞凋亡性细胞死亡途径的治疗在凋亡缺陷型肿瘤细胞中显示出更高的治疗成功率。利用工程纳米粒子的多功能特性，可能使癌症治疗能够针对尚未探索的途径，如铁死亡、自噬和坏死性凋亡。坏死性凋亡是一种由半胱天冬酶非依赖性的相同凋亡死亡信号引发的程序性坏死，而自噬是一种自我降解的过程，导致空泡化，铁死亡是一种由脂质过氧化驱动的铁依赖性形式。针对这些严格调控的非细胞凋亡途径可能成为癌症药物开发、诊断和新型癌症纳米治疗的新方向。本综述强调了当前的挑战以及该研究领域的进展，并最终从临床价值方面总结了未来的前景。
