Ponton-Almodovar Adriana, Sanderson Samuel, Rattan Ramandeep, Bernard Jamie J, Horibata Sachi
Precision Health Program, Michigan State University, East Lansing, MI 48824, USA.
Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
Cancer Drug Resist. 2024 Dec 17;7:53. doi: 10.20517/cdr.2024.111. eCollection 2024.
Ovarian cancer is one of the deadliest gynecologic cancers affecting the female reproductive tract. This is largely attributed to frequent recurrence and development of resistance to the platinum-based drugs cisplatin and carboplatin. One of the major contributing factors to increased cancer progression and resistance to chemotherapy is the tumor microenvironment (TME). Extracellular signaling from cells within the microenvironment heavily influences progression and drug resistance in ovarian cancer. This is frequently done through metabolic reprogramming, the process where cancer cells switch between biochemical pathways to increase their chances of survival and proliferation. Here, we focus on how crosstalk between components of the TME and the tumor promotes resistance to platinum-based chemotherapy. We highlight the role of cancer-associated fibroblasts, immune cells, adipocytes, and endothelial cells in ovarian tumor progression, invasion, metastasis, and chemoresistance. We also highlight recent advancements in targeting components of the TME as a novel therapeutic avenue to combat chemoresistance in ovarian cancer.
卵巢癌是影响女性生殖道的最致命的妇科癌症之一。这在很大程度上归因于铂类药物顺铂和卡铂的频繁复发和耐药性发展。肿瘤微环境(TME)是导致癌症进展加快和化疗耐药的主要因素之一。微环境中细胞的细胞外信号严重影响卵巢癌的进展和耐药性。这通常是通过代谢重编程来实现的,代谢重编程是癌细胞在生化途径之间切换以增加其存活和增殖机会的过程。在这里,我们关注TME的组成部分与肿瘤之间的相互作用如何促进对铂类化疗的耐药性。我们强调癌症相关成纤维细胞、免疫细胞、脂肪细胞和内皮细胞在卵巢肿瘤进展、侵袭、转移和化疗耐药中的作用。我们还强调了针对TME组成部分作为对抗卵巢癌化疗耐药性的新治疗途径的最新进展。