Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

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.

Dysregulation of Peripheral Blood Mononuclear Cells and Immune-Related Proteins during the Early Post-Operative Immune Response in Ovarian Cancer Patients

“…Given the challenges in OC treatment, such as chemoresistance [ 63 ] and frequent disease relapse [ 6 ], we propose that the early post-operative period presents a valuable opportunity to enhance concurrent treatment strategies. These could include systemic intraoperative chemotherapy or hyperthermic intraperitoneal chemotherapy [ 7 , 76 ]. The establishment of patient selection criteria based on PBMC activity in the early post-operative phase could also play a pivotal role in developing new treatments and refining existing treatment modalities for OC patients.…”

“…Nevertheless, even with the most effective surgical strategies and chemotherapy protocols, disease relapse is frequent, and long-term remission remains a challenge [ 6 ]. Consequently, both established and novel approaches are continually being investigated in the quest to improve treatment strategies [ 7 , 8 ].…”

Knockdown of CENPM activates cGAS-STING pathway to inhibit ovarian cancer by promoting pyroptosis

“…In the advanced stages of OC, cancer cells spread from the ovaries to the pelvis, abdomen, lungs, or multiple secondary sites, which severely limits the efficacy of treatment options that cause fatal clinical outcomes [ 6 ]. Currently, platinum-based chemotherapy is the mainstream treatment for OC [ 7 ]. Although improved surgical techniques and intensive chemotherapy regimens have improved survival in patients with advanced OC over the past two decades, treatment with non-selective cytotoxic drugs often results in severe toxic effects and transient antitumor responses [ 8 ].…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…In modern medicine, the understanding of metal-ion functions [ 22 ] and diagnosis at the molecular level [ 23 ] have become inevitable consequences of delivering new MBD in medicinal bioinorganic chemistry [ 24 , 25 ]. There is still inadequate effort devoted at mechanistic levels [ 26 ] towards providing an alternative, targeted, and rational approach [ 27 ] to supplement screening of novel chemical entities for biological activity [ 21 ].…”