Pancreatic cancer (PC) remains a leading cause of mortality worldwide due to the absence of early detection methods and the low success rates of traditional therapeutic strategies. Drug resistance in PC is driven by its desmoplastic stroma, which creates a barrier that shields cancer niches and prevents the penetration of drugs. The PC stroma comprises heterogeneous cellular populations and non-cellular components involved in aberrant ECM deposition, immunosuppression, and drug resistance. These components can influence PC development through intricate and complex crosstalk with the PC cells. Understanding how stromal components and cells interact with and influence the invasiveness and refractoriness of PC cells is thus a prerequisite for developing successful stroma-modulating strategies capable of remodeling the PC stroma to alleviate drug resistance and enhance therapeutic outcomes. In this review, we explore how non-cellular and cellular stromal components, including cancer-associated fibroblasts and tumor-associated macrophages, contribute to the immunosuppressive and tumor-promoting effects of the stroma. We also examine the signaling pathways underlying their activation, tumorigenic effects, and interactions with PC cells. Finally, we discuss recent pre-clinical and clinical work aimed at developing and testing novel stroma-modulating agents to alleviate drug resistance and improve therapeutic outcomes in PC.

由于缺乏早期检测方法和传统治疗策略的成功率较低，胰腺癌（PC）仍然是全球死亡的主要原因。PC 的耐药性是由其促纤维增生基质驱动的，该基质会形成屏障，保护癌症微环境并阻止药物渗透。PC 基质包含异质细胞群和非细胞成分，参与异常ECM沉积、免疫抑制和耐药性。这些组件可以通过与 PC 细胞错综复杂的串扰影响 PC 的发育。因此，了解基质成分和细胞如何与 PC 细胞相互作用并影响 PC 细胞的侵袭性和难治性，是开发成功的基质调节策略的先决条件，该策略能够重塑 PC 基质，以减轻耐药性并增强治疗效果。在这篇综述中，我们探讨了非细胞和细胞基质成分，包括癌症相关成纤维细胞和肿瘤相关巨噬细胞，如何促进基质的免疫抑制和肿瘤促进作用。我们还研究了其激活、致瘤作用以及与 PC 细胞相互作用的信号通路。最后，我们讨论了最近的临床前和临床工作，旨在开发和测试新型基质调节剂，以减轻 PC 的耐药性并改善治疗结果。