Eckert Mark A, Orozco Carlos, Xiao Jason, Javellana Melissa, Lengyel Ernst
Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, USA.
Cancers (Basel). 2021 Jun 23;13(13):3136. doi: 10.3390/cancers13133136.
High-grade serous ovarian cancer (HGSOC) is characterized by a complex and dynamic tumor microenvironment (TME) composed of cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, and adipocytes. Although most approved therapies target cancer cells, a growing body of evidence suggests that chemotherapeutic agents have an important role in regulating the biology of the diverse cells that compose the TME. Understanding how non-transformed cells respond and adapt to established therapeutics is necessary to completely comprehend their action and develop novel therapeutics that interrupt undesired tumor-stroma interactions. Here, we review the effects of chemotherapeutic agents on normal cellular components of the host-derived TME focusing on CAFs. We concentrate on therapies used in the treatment of HGSOC and synthesize findings from studies focusing on other cancer types and benign tissues. Agents such as platinum derivatives, taxanes, and PARP inhibitors broadly affect the TME and promote or inhibit the pro-tumorigenic roles of CAFs by modifying the bidirectional cross-talk between tumor and stromal cells in the tumor organ. While most chemotherapy research focuses on cancer cells, these studies emphasize the need to consider all cell types within the tumor organ when evaluating chemotherapeutics.
高级别浆液性卵巢癌（HGSOC）的特征是具有复杂且动态的肿瘤微环境（TME），该微环境由癌症相关成纤维细胞（CAF）、免疫细胞、内皮细胞和脂肪细胞组成。尽管大多数获批的疗法靶向癌细胞，但越来越多的证据表明，化疗药物在调节构成TME的多种细胞的生物学特性方面具有重要作用。了解未转化细胞如何对既定疗法作出反应并适应这些疗法，对于全面理解其作用以及开发能够中断不良肿瘤-基质相互作用的新型疗法而言是必要的。在此，我们综述化疗药物对宿主来源的TME中正常细胞成分的影响，重点关注CAF。我们聚焦于用于治疗HGSOC的疗法，并综合来自针对其他癌症类型和良性组织的研究结果。铂类衍生物、紫杉烷和聚（ADP-核糖）聚合酶（PARP）抑制剂等药物广泛影响TME，并通过改变肿瘤器官中肿瘤细胞与基质细胞之间的双向相互作用，促进或抑制CAF的促肿瘤作用。虽然大多数化疗研究聚焦于癌细胞，但这些研究强调在评估化疗药物时需要考虑肿瘤器官内的所有细胞类型。
