摘要
Abstract Background: In the clinical setting, anticancer therapy is routinely administered to stimulate programmed cell death or “apoptosis.” The goal is to eliminate tumor cells. Whether selective activation of apoptosis facilitates aggressive disease relapse in the longer term is still unaddressed. Apoptosis defects have a crucial role in cancer progression and carcinogenesis. Thus, targeting apoptosis may be important in developing new cancer therapeutic modalities Methods: We summarize the shift in thinking that, while apoptosis is a barrier to oncogenesis, it paradoxically drives cancer formation and progression when executed incompletely, i.e., sublethal apoptosis. Also, we review apoptotic mechanisms, the role of apoptosis in carcinogenesis, and how it contributes to cancer treatment. Result and Conclusion: Most current research focuses on the extent of cell death in vitro, but no evidence exists that protein regulation of cell death in vitro is similar to what happens in vivo. Future research requires identifying targets upstream and downstream of such proteins through identifying protein-protein interactions in different survival/apoptosis pathways. Finding nexuses where such pathways interconnect is critical, along with possible mechanisms for regulation. 背景:在临床环境中,抗癌疗法通常用于刺激程序性细胞死亡或“细胞凋亡”。目标是消除肿瘤细胞。从长远来看,细胞凋亡的选择性激活是否会促进侵袭性疾病复发仍未得到解决。细胞凋亡缺陷在癌症进展和致癌作用中起着至关重要的作用。因此,靶向细胞凋亡可能对开发新的癌症治疗方式很重要。 方法:我们总结了这一想法的转变,即虽然细胞凋亡是肿瘤发生的障碍,但当不完全执行时,它会自相矛盾地驱动癌症的形成和进展,即亚致死细胞凋亡。此外,我们还回顾了细胞凋亡机制、细胞凋亡在致癌作用中的作用,以及它如何促进癌症治疗。 结果与结论:目前大多数研究都集中在体外细胞死亡的程度,但没有证据表明体外细胞死亡的蛋白质调节与体内发生的情况相似。未来的研究需要通过识别不同存活/凋亡途径中的蛋白质-蛋白质相互作用来识别此类蛋白质的上游和下游靶点。寻找这些途径相互连接的联系至关重要,以及可能的监管机制。
关键词: 程序性细胞死亡、细胞凋亡、抗癌、蛋白质治疗、免疫治疗、基因治疗。
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