Hsu Sheng-Kai, Chu Yi-Hsuan, Syue Wun-Jyun, Lin Hugo You-Hsien, Chang Wen-Tsan, Chen Jeff Yi-Fu, Wu Chang-Yi, Yen Chia-Hung, Cheng Kai-Chun, Chiu Chien-Chih
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Front Oncol. 2022 May 19;12:872883. doi: 10.3389/fonc.2022.872883. eCollection 2022.
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, with a dismal 5-year survival rate of less than 10%. It is estimated that approximately 80% of pancreatic ductal carcinoma (PDAC) patients are diagnosed at an advanced or metastatic stage. Hence, most patients are not appropriate candidates for surgical resection and therefore require systemic chemotherapy. However, it has been reported that most patients develop chemoresistance within several months, partly because of antiapoptotic mechanisms. Hence, inducing alternative programmed cell death (PCD), including ferroptosis, necroptosis or pyroptosis, seems to be a promising strategy to overcome antiapoptosis-mediated chemoresistance. In this review, we shed light on the molecular mechanisms of ferroptosis, necroptosis and pyroptosis and suggest several potential strategies (e.g., compounds and nanoparticles [NPs]) that are capable of triggering nonapoptotic PCD to suppress PDAC progression. In conclusion, these strategies might serve as adjuvants in combination with clinical first-line chemotherapies to improve patient survival rates.
胰腺导管腺癌（PDAC）是最致命的癌症，其5年生存率低至不到10%，令人沮丧。据估计，约80%的胰腺导管癌（PDAC）患者在晚期或转移阶段被诊断出来。因此，大多数患者不适合进行手术切除，因此需要全身化疗。然而，据报道，大多数患者在几个月内就会产生化疗耐药性，部分原因是抗凋亡机制。因此，诱导包括铁死亡、坏死性凋亡或细胞焦亡在内的替代性程序性细胞死亡（PCD），似乎是克服抗凋亡介导的化疗耐药性的一种有前景的策略。在这篇综述中，我们阐明了铁死亡、坏死性凋亡和细胞焦亡的分子机制，并提出了几种能够触发非凋亡性PCD以抑制PDAC进展的潜在策略（例如化合物和纳米颗粒 [NPs]）。总之，这些策略可能作为辅助手段与临床一线化疗联合使用，以提高患者生存率。
