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攻克胰腺癌的化疗耐药性:在间质纤维化和缺氧环境中探索新的药物治疗和递药方法。

Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia.

机构信息

Department of Pharmaceutics, GITAM School of Pharmacy, GITAM (Deemed to be University), Rudraram, 502329 Telangana, India.

Aditya Pharmacy College, Surampalem, 533437, Andhra Pradesh, India.

出版信息

Cancer Lett. 2024 Apr 28;588:216782. doi: 10.1016/j.canlet.2024.216782. Epub 2024 Mar 6.

Abstract

Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer.

摘要

胰腺癌在肿瘤学领域构成了重大挑战,其原因在于其侵袭性行为、有限的治疗选择和不利的预后。在 5 年的时间里,仅有 10%的存活率,因此寻找有效的干预措施变得更加紧迫。肿瘤微环境中纤维组织增生和缺氧之间的复杂关系通过促进对化疗的耐药性和阻碍治疗效果进一步使问题复杂化。纤维组织增生特有的致密细胞外基质和癌相关成纤维细胞形成了物理和生化屏障,阻碍药物渗透并促进免疫抑制环境。同时,缺氧促进了侵袭性肿瘤行为和对传统治疗的耐药性。本文全面探讨了新兴药物和创新药物输送方法。值得注意的是,基于纳米颗粒的输送系统、局部药物输送植入物和携氧策略的进展因其增强药物可及性和治疗效果的潜力而受到关注。这些策略与传统化疗和靶向药物的结合显示出协同作用的潜力,从而增强了治疗反应。这些新兴干预措施可以减轻纤维组织增生和缺氧引起的障碍,提高胰腺癌的药物输送、治疗效果和患者预后。本文深入探讨了新兴抗癌药物和创新药物输送策略的动态领域,这些策略有望克服纤维组织增生和缺氧对胰腺癌治疗带来的挑战。

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