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.
Keywords: PARP inhibitors; cancer therapy; cancer-associated fibroblasts; carboplatin; ovarian cancer; review; stroma; taxanes; tumor microenvironment.