胰管腺癌（PDAC）是一种高度威胁生命的肿瘤，具有早期发现率低、快速进展并易产生对化疗的抗药性的倾向。因此，了解胰腺癌发生、发展和转移的调控机制对于提高治疗效果至关重要。在本综述中，我们总结了与PDAC相关的单基因突变（包括KRAS、CDKN2A、TP53、SMAD4和其他不太常见的突变）、表观遗传变化（包括DNA甲基化、组蛋白修饰和RNA干扰）以及大的染色体改变（如拷贝数变异、染色体重排和染色体碎裂）等。此外，我们还讨论了在PDAC中作为中间致癌因子的信号通路的变异，包括PI3K/AKT、MAPK/ERK、Hippo和TGF-β信号通路。本综述的重点是研究PDAC微环境的变化，特别是免疫抑制细胞、癌相关成纤维细胞、淋巴细胞、其他旁癌细胞和肿瘤细胞外基质在肿瘤进展中的作用。已有研究报道胰腺的周围神经轴突在癌症发展中发挥着关键作用。此外，肿瘤细胞通过分泌特定因子能够影响周围非肿瘤细胞的行为，无论是局部还是远距离。在本综述中，我们阐明了PDAC进展过程中细胞内分子和细胞外环境的变化。总的来说，本综述可以增进对PDAC的生物学特性的理解，并指导更精确的治疗策略的发展。版权所有 © 2023 Elsevier B.V.出版。

Pancreatic ductal adenocarcinoma (PDAC) is a highly life-threatening tumour with a low early-detection rate, rapid progression and a tendency to develop resistance to chemotherapy. Therefore, understanding the regulatory mechanisms underlying the initiation, development and metastasis of pancreatic cancer is necessary for enhancing therapeutic effectiveness. In this review, we summarised single-gene mutations (including KRAS, CDKN2A, TP53, SMAD4 and some other less prevalent mutations), epigenetic changes (including DNA methylation, histone modifications and RNA interference) and large chromosome alterations (such as copy number variations, chromosome rearrangements and chromothripsis) associated with PDAC. In addition, we discussed variations in signalling pathways that act as intermediate oncogenic factors in PDAC, including PI3K/AKT, MAPK/ERK, Hippo and TGF-β signalling pathways. The focus of this review was to investigate alterations in the microenvironment of PDAC, particularly the role of immunosuppressive cells, cancer-associated fibroblasts, lymphocytes, other para-cancerous cells and tumour extracellular matrix in tumour progression. Peripheral axons innervating the pancreas have been reported to play a crucial role in the development of cancer. In addition, tumour cells can influence the behaviour of neighbouring non-tumour cells by secreting certain factors, both locally and at a distance. In this review, we elucidated the alterations in intracellular molecules and the extracellular environment that occur during the progression of PDAC. Altogether, this review may enhance the understanding of the biological characteristics of PDAC and guide the development of more precise treatment strategies.Copyright © 2023. Published by Elsevier B.V.