Genetics and biology of pancreatic ductal adenocarcinoma

IF 7.5 1区 生物学 Q1 CELL BIOLOGY Genes & development Pub Date : 2024-11-07 DOI:10.1101/gad.351863.124
Haoqiang Ying, Alec C. Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A. DePinho
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Abstract

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.
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胰腺导管腺癌的遗传学和生物学特性
胰腺导管腺癌(PDAC)给患者带来了严峻的预后。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,为靶向疗法和免疫疗法的合理开发奠定了基础。在此,我们回顾了 PDAC 的基因组图谱、特定致癌事件在肿瘤发生和发展过程中的作用,以及它们对形成肿瘤生物学的贡献。我们进一步总结和归纳了单细胞和代谢分析技术的突破性进展,这些进展揭示了 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细胞和基质细胞之间的代谢交叉对话。这些概念上的进步催生了新的免疫疗法方案,尤其是癌症疫苗,目前这些方案已进入临床试验阶段。我们还强调了 KRAS 靶向治疗的出现,这是一个里程碑式的进步,它改变了治疗模式,并为免疫疗法和靶向策略的结合提供了一个平台。本综述从一个视角总结了 PDAC 领域在这一重大拐点上当前面临的科学和治疗挑战以及改变实践的机遇。
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来源期刊
Genes & development
Genes & development 生物-发育生物学
CiteScore
17.50
自引率
1.90%
发文量
71
审稿时长
3-6 weeks
期刊介绍: Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers. Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).
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