Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

SIMPLE SUMMARY: Advanced ovarian cancer is the leading cause of gynecological death with a high rate of reoccurrence indicating the critical need for improved therapeutics. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment for ovarian cancer has shown efficacy in extending patient overall survival yet the mechanism of benefit remains unknown. The aim of this review is to address the impact of hyperthermia, providing insights into HIPEC efficacy. Here we review reports of HIPEC treatment in ovarian and peritoneal cancers as well as discussion of animal models used for emulating clinical HIPEC. ABSTRACT: Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy, yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer, though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage, impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.