A Narrative Review of In Vivo Studies on the Role of Reactive Oxygen Species in Ovarian Cancer

In ovarian cancer, reactive oxygen species (ROS) are both toxic byproducts and mediators of signaling and stress adaptation, such that the same “ROS change” can suppress or promote tumors in vivo. Here, we integratively summarize how ROS modulation reshapes tumor growth, metastasis, and treatment response in ovarian cancer, based on 22 original in vivo-containing studies that were selected from a five-database search of papers published from January 1990 to December 2025. On the antitumor axis, ROS amplification in xenograft models is accompanied by reduced tumor burden and increased markers of cell death, and can operate through diverse death programs beyond apoptosis, including pyroptosis and ferroptosis. ROS-based anticancer effects may vary depending on whether cytoprotective autophagy is co-induced. For example, in models treated with daphnetin, ROS-dependent cell death occurs together with induction of cytoprotective autophagy and the anticancer effect is strengthened when an autophagy inhibitor is added. In a therapeutic context, autophagy may thus function as an adaptive response in tumor cells to partially buffer ROS-induced stress. Conversely, on the pro-tumor axis, ROS can serve as an upstream signal driving inflammatory and metastatic processes. In a peritoneal metastasis model, GPX1 inhibition-induced ROS elevation was linked to increased metastatic burden. In the context of drug resistance, platinum resistance is proposed to be an adaptive state shaped not by the absolute level of ROS alone, but by integrated ROS-sensing and buffering circuits, the DNA damage response (DDR), and NF-κB networks. In vivo, AMPK–ROS axis activation through ACLY inhibition or resetting of drug responsiveness can be connected to tumor suppression and increased sensitivity. Furthermore, ROS modulation is not limited to tumor cell-intrinsic targets: it can also be linked to therapeutic response reprogramming at the tumor microenvironment (TME) level, such as via regulation of acidity/ROS conditions and coupling to macrophage polarization in immunocompetent syngeneic models. Taken together, these lines of in vivo evidence indicate that, in ovarian cancer, ROS should not be interpreted in a binary “increase/decrease” manner, but rather in terms of redox-buffering capacity, the engaged signaling axes (cell death, DDR, metastasis/inflammation), and interactions with TME factors.