Leeds Institute of Medical Research at St James's, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, United Kingdom.
Leeds Institute of Medical Research at St James's, St James's University Hospital, Beckett Street, Leeds, LS9 7TF, United Kingdom; St James's Institute of Oncology, Bexley Wing, Beckett Street, Leeds, LS9 7TF, United Kingdom.
Semin Cancer Biol. 2021 Dec;77:3-28. doi: 10.1016/j.semcancer.2021.02.007. Epub 2021 Feb 16.
Ovarian cancer typically presents at an advanced stage, and although the majority of cases initially respond well to platinum-based therapies, chemoresistance almost always occurs leading to a poor long-term prognosis. While various cellular autonomous mechanisms contribute to intrinsic or acquired platinum resistance, the tumour microenvironment (TME) plays a central role in resistance to therapy and disease progression by providing cancer stem cell niches, promoting tumour cell metabolic reprogramming, reducing chemotherapy drug perfusion and promoting an immunosuppressive environment. As such, the TME is an attractive therapeutic target which has been the focus of intense research in recent years. This review provides an overview of the unique ovarian cancer TME and its role in disease progression and therapy resistance, highlighting some of the latest preclinical and clinical data on TME-targeted therapies. In particular, it focuses on strategies targeting cancer-associated fibroblasts, tumour-associated macrophages, cancer stem cells and cancer cell metabolic vulnerabilities.
卵巢癌通常在晚期出现，尽管大多数病例最初对铂类治疗反应良好，但几乎总是会发生化疗耐药，导致预后不良。虽然各种细胞自主机制有助于内在或获得性铂耐药，但肿瘤微环境 (TME) 通过提供癌症干细胞龛、促进肿瘤细胞代谢重编程、减少化疗药物灌注和促进免疫抑制环境，在对治疗和疾病进展的耐药性中起着核心作用。因此，TME 是一个有吸引力的治疗靶点，近年来一直是密集研究的焦点。这篇综述概述了独特的卵巢癌 TME 及其在疾病进展和治疗耐药性中的作用，重点介绍了一些最新的 TME 靶向治疗的临床前和临床数据。特别是，它侧重于针对癌相关成纤维细胞、肿瘤相关巨噬细胞、癌症干细胞和癌细胞代谢脆弱性的策略。
