Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and stromal cells that sustains anabolic growth and suppresses tumor immunity. These conceptual advances have generated novel immunotherapy regimens, particularly cancer vaccines, which are now in clinical testing. We also highlight the advent of KRAS targeted therapy, a milestone advance that has transformed treatment paradigms and offers a platform for combined immunotherapy and targeted strategies. This review provides a perspective summarizing current scientific and therapeutic challenges as well as practice-changing opportunities for the PDAC field at this major inflection point.

中文翻译：

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胰腺导管腺癌的遗传学和生物学


胰腺导管腺癌 （PDAC） 对患者的预后很严峻。最近的多学科研究工作为其遗传学和肿瘤生物学提供了重要见解，为靶向和免疫疗法的合理开发奠定了基础。在这里，我们回顾了 PDAC 基因组景观和特定致癌事件在肿瘤发生和进展中的作用，以及它们对塑造其肿瘤生物学的贡献。我们进一步总结和综合了单细胞和代谢分析技术的突破，这些技术阐明了 PDAC 肿瘤微环境的复杂细胞组成和异型相互作用，重点是维持合成代谢生长和抑制肿瘤免疫的癌症和基质细胞之间的代谢串扰。这些概念上的进步产生了新的免疫治疗方案，特别是癌症疫苗，目前正在进行临床试验。我们还强调了 KRAS 靶向治疗的出现，这是一项里程碑式的进步，它改变了治疗范式，并为免疫治疗和靶向策略的联合提供了一个平台。本综述提供了一个观点，总结了当前的科学和治疗挑战，以及 PDAC 领域在这个主要转折点上改变实践的机会。