Development of a noninvasive murine model of hyperthermic intraperitoneal chemotherapy (HIPEC) treatment for ovarian cancer

Ovarian cancer (OC) is currently the leading cause of death from gynecological cancer, with 60% of cases ending in mortality. As an aggressive disease of the female reproductive system, OC in the advanced stage metastasizes to the peritoneum, and ascites is present in > 90% of patients with stage III-IV disease. This accumulation of fluid in the abdomen is associated with a 5% survival rate. Current therapeutic strategies exist for treating OC, yet tumors recur and become chemoresistance, indicating a critical need for improved therapeutics. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a successful treatment given to select patients with advanced disease. HIPEC involves pumping heated chemotherapy throughout the peritoneal cavity at time of debulking surgery. HIPEC has shown success in treating advanced OC by extending overall survival by nearly 12 months, yet the mechanisms of benefit remain unknown. A rapid noninvasive animal model is lacking for the study of HIPEC. This poses a significant barrier for improving HIPEC protocols for patient benefit. We have developed the first noninvasive animal model by using external abdominal heat with chemotherapy. Results reveal significant attenuation of tumor growth, delayed tumor-associated ascites development, and extended survival after treatment with hyperthermic chemotherapy compared to normothermic cisplatin treatment. This method is rapidly allowing for multiple mouse treatments per procedure. Our findings show hyperthermic chemotherapy delays ascites onset and extend survival. This non-invasive model allows for implementation of mechanistic studies to investigate HIPEC survival benefit. Elucidating these mechanisms is essential to enhance HIPEC benefit and identifying strategies to define less invasive therapeutic mechanisms for the treatment of ovarian cancer.