Abstract
In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects in HR systems are associated more frequently with higher tumor infiltrating lymphocytes, providing a rationale for developing combination therapy with immune-modulating agents and PARP inhibitors. Again, locoregional therapies combining heat shock and chemotherapy delivery have been shown to induce an anticancer immune response in vitro. Thus, the potential for locoregional therapeutic approaches that may impact the immune system, perhaps in combination with immune-modulating agents or PARP inhibitors, needs to be further explored. With this premise, we reviewed the main biological and clinical data demonstrating a strict interplay between the immune system, DNA repair mechanisms, and intraperitoneal therapies in ovarian cancer, with a focus on potential future therapeutic implications.
Highlights
Ovarian cancer is the second cause of death from gynecological malignancies, and the seventh most common cause of cancer death worldwide [1]
The proposed advantages of hyperthermic intraperitoneal chemotherapy (HIPEC) over intraperitoneal administration are a single-dose approach with direct observation of intraoperative drug exposure, without the risk of barriers due to postoperative adhesions, and a high-proportion cisplatin dose absorbed by target tumor cells; hyperthermia that has been shown to increase tumor penetration of chemotherapy, and enhances cyotoxicity synergistically [77]
Ovarian cancer is strongly linked to defects in DNA repair mechanisms
Summary
Ovarian cancer is the second cause of death from gynecological malignancies, and the seventh most common cause of cancer death worldwide [1]. The most common ovarian neoplasm is a high-grade serous histological subtype, accounting for about 70% of cases and causing the majority (90%) of ovarian cancer deaths. Stage III or IV mucinous ovarian cancer patients have a poorer prognosis than women with other, more common subtypes ( serous or endometrioid ovarian cancer), and may be related to a poorer response to chemotherapy [7]. High-grade serous ovarian cancer is frequently associated with DNA repair deficiencies [8]. The finding that ovarian-related PC is a regional disease rather than a systemic disease has led to the development of locoregional approaches to improve ovarian cancer patient outcome In this context, intraperitoneal chemotherapy, endowing direct exposure of chemotherapy to the peritoneal surface plus intravenous chemotherapy, compared with intravenous chemotherapy alone after complete or optimal primary cytoreductive surgery (CRS), showed a 16-month increase in survival. In this review, we analyze the strict interplay between DNA repair pathway alterations, the immune system, and inflammation in an attempt to identify unique challenges and opportunities for new treatment strategies
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