Mohana Chakkera , Jeremy B. Foote , Batoul Farran , Ganji Purnachandra Nagaraju
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引用次数: 0
摘要
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)仍然是导致全球死亡的主要原因。胰腺癌的耐药性是由其脱膜基质驱动的,脱膜基质会形成一道屏障,保护癌症龛位并阻止药物渗透。PC 基质由异质性细胞群和非细胞成分组成,参与 ECM 的异常沉积、免疫抑制和耐药性。这些成分可通过与 PC 细胞之间错综复杂的相互作用影响 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其侵袭性和耐药性是开发成功的基质调节策略的先决条件,这些策略能够重塑 PC 基质,从而减轻耐药性并提高治疗效果。在这篇综述中,我们将探讨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。我们还研究了它们激活、致瘤效应以及与 PC 细胞相互作用的信号通路。最后,我们将讨论近期旨在开发和测试新型基质调节药物的临床前和临床工作,以减轻耐药性并改善 PC 的治疗效果。
Breaking the stromal barrier in pancreatic cancer: Advances and challenges
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.
期刊介绍:
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.