文章：

近期抗KRASG12D疗法：胰腺导管腺癌的“可能之不可能”

Recent Anti-KRASG12DTherapies: A “Possible Impossibility” for Pancreatic Ductal Adenocarcinoma

原文发布日期：19 February 2025

DOI: 10.3390/cancers17040704

类型: Article

开放获取: 是

英文摘要：

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, able to thrive in a challenging tumor microenvironment. Current standard therapies, including surgery, radiation, chemotherapy, and chemoradiation, have shown a dismal survival prognosis, resulting in less than a year of life in the metastatic setting.Methods: The pressing need to find better therapeutic methods brought about the discovery of new targeted therapies against the infamousKRASmutations, the major oncological drivers of PDAC.Results: The most commonKRASmutation isKRASG12D, which causes a conformational change in the protein that constitutively activates downstream signaling pathways driving cancer hallmarks. Novel anti-KRASG12Dtherapies have been developed for solid-organ tumors, including small compounds, pan-RAS inhibitors, protease inhibitors, chimeric T cell receptors, and therapeutic vaccines.Conclusions: This comprehensive review summarizes current knowledge on the biology ofKRAS-driven PDAC, the latest therapeutic options that have been experimentally validated, and developments in ongoing clinical trials.

摘要翻译： 

背景：胰腺导管腺癌（PDAC）是一种侵袭性癌症，能够在具有挑战性的肿瘤微环境中生长。目前的标准疗法，包括手术、放疗、化疗和放化疗，其生存预后均不理想，在转移性情况下患者生存期不足一年。 方法：寻找更佳治疗方法的迫切需求促使人们发现了针对臭名昭著的KRAS突变的新型靶向疗法，该突变是PDAC的主要致癌驱动因素。 结果：最常见的KRAS突变是KRASG12D，它会导致蛋白质构象改变，从而持续激活驱动癌症特征的下游信号通路。针对实体器官肿瘤的新型抗KRASG12D疗法已得到开发，包括小分子化合物、泛RAS抑制剂、蛋白酶抑制剂、嵌合T细胞受体以及治疗性疫苗。 结论：本综述全面总结了当前关于KRAS驱动型PDAC的生物学知识、经实验验证的最新治疗方案以及正在进行中的临床试验进展。

原文链接：

Recent Anti-KRASG12DTherapies: A “Possible Impossibility” for Pancreatic Ductal Adenocarcinoma