Duan Hongtao, Gao Li, Asikaer Aiminuer, Liu Lingzhi, Huang Kuilong, Shen Yan
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 405400, People's Republic of China.
Mol Biotechnol. 2025 Apr;67(4):1463-1482. doi: 10.1007/s12033-024-01131-8. Epub 2024 Apr 4.
Pancreatic cancer stands as one of the most lethal malignancies, characterized by delayed diagnosis, high mortality rates, limited treatment efficacy, and poor prognosis. Disulfidptosis, a recently unveiled modality of cell demise induced by disulfide stress, has emerged as a critical player intricately associated with the onset and progression of various cancer types. It has emerged as a promising candidate biomarker for cancer diagnosis, prognosis assessment, and treatment strategies. In this study, we have effectively established a prognostic risk model for pancreatic cancer by incorporating multiple differentially expressed long non-coding RNAs (DElncRNAs) closely linked to disulfide-driven cell death. Our investigation delved into the nuanced relationship between the DElncRNA-based predictive model for disulfide-driven cell death and the therapeutic responses to anticancer agents. Our findings illuminate that the high-risk subgroup exhibits heightened susceptibility to the small molecule compound AZD1208, positioning it as a prospective therapeutic agent for pancreatic cancer. Finally, we have elucidated the underlying mechanistic potential of AZD1208 in ameliorating pancreatic cancer through its targeted inhibition of the peroxisome proliferator-activated receptor-γ (PPARG) protein, employing an array of comprehensive analytical methods, including molecular docking and molecular dynamics (MD) simulations. This study explores disulfidptosis-related genes, paving the way for the development of targeted therapies for pancreatic cancer and emphasizing their significance in the field of oncology. Furthermore, through computational biology approaches, the drug AZD1208 was identified as a potential treatment targeting the PPARG protein for pancreatic cancer. This discovery opens new avenues for exploring targets and screening drugs for pancreatic cancer.
胰腺癌是最致命的恶性肿瘤之一，其特点是诊断延迟、死亡率高、治疗效果有限且预后不良。二硫键诱导的细胞焦亡是一种最近发现的由二硫键应激诱导的细胞死亡方式，已成为与各种癌症类型的发生和发展密切相关的关键因素。它已成为癌症诊断、预后评估和治疗策略中有前景的候选生物标志物。在本研究中，我们通过纳入多个与二硫键驱动的细胞死亡密切相关的差异表达长链非编码RNA（DElncRNAs），有效地建立了胰腺癌的预后风险模型。我们的研究深入探讨了基于DElncRNA的二硫键驱动细胞死亡预测模型与抗癌药物治疗反应之间的细微关系。我们的研究结果表明，高危亚组对小分子化合物AZD1208表现出更高的敏感性，使其成为胰腺癌的一种潜在治疗药物。最后，我们通过一系列综合分析方法，包括分子对接和分子动力学（MD）模拟，阐明了AZD1208通过靶向抑制过氧化物酶体增殖物激活受体-γ（PPARG）蛋白来改善胰腺癌的潜在机制。本研究探索了与二硫键诱导的细胞焦亡相关的基因，为胰腺癌靶向治疗的发展铺平了道路，并强调了它们在肿瘤学领域的重要性。此外，通过计算生物学方法，确定药物AZD1208是一种针对胰腺癌PPARG蛋白的潜在治疗药物。这一发现为探索胰腺癌的靶点和筛选药物开辟了新途径。
