Advances in Ovarian Cancer Therapeutics

Ovarian cancer is the most lethal of all gynecologic malignancies, due to the fact that the majority of patients are diagnosed at an advanced stage where disease has already begun to metastasize. Furthermore, even though many patients achieve remission following frontline platinum-taxane based chemotherapy, approximately 12-18 months later, patients experience a recurrence in which their tumor is no longer responsive to traditional therapeutic approaches. In addition, while target treatments, such as immunotherapies, have revolutionized the field of oncology within the past decade, the majority of ovarian cancer patients have been largely unresponsive to these clinically available therapies. Despite this fact, ovarian cancer is considered to be an immune responsive cancer as it has been extensively documented that intratumoral lymphocytes are significantly associated with improved patient clinical outcomes. Therefore, a clinical need exists to develop immunotherapies that take into account the unique and complex immunosuppressive nature of the ovarian tumor microenvironment.

Conversely as the field of ovarian cancer research has grown to appreciate the vast genomic and molecular heterogeneity of the disease, this has led to the breakthrough of poly (ADP-ribose) polymerase (PARP) inhibitors for homologous recombination deficient patients. The incorporation of PARP inhibitors as standard of care in the maintenance setting has led to a significant improvement in overall survival outcomes for this patient population. However, despite this therapeutic advancement there remains a number of patients that become resistant to PARP therapies. Therefore, understanding how to overcome PARP resistance, as well the development of targeted therapies for homologous recombination proficient patients have become two new challenges that warrant further investigation.

This Research Topic encourages submissions that address novel therapeutic advances in ovarian cancer that improve immunotherapy response and address critical challenges in the field such as chemotherapy and PARP resistance. In addition, drug discovery approaches that consider the specific genomic and molecular phenotypes of ovarian cancer patients—such as those that led to the FDA approval of PARP inhibitors—need to be replicated for other ovarian cancer molecular subtypes. Finally, as the development of novel digital spatial profiling tools have emerged, studies that marry transcriptomics with intratumoral location will produce high quality clinically translatable data that can lead to important targeted therapeutic breakthroughs in ovarian cancer.

This Research Topic includes but is not limited to the following themes:

• New immunomodulatory therapeutic approaches.

• Predictive markers of prognosis and therapeutic response.

• Adoptive cell therapies.

• Antibody-drug conjugates.

• Strategies to overcome chemotherapy or PARP resistance.

• Novel combinatorial combinations with standard of care ovarian cancer therapies.

• Therapies that target specific molecular or genomic subtypes of ovarian cancer.

• Mechanisms of therapy resistance.

• Bioinformatic analyses of the ovarian tumor immune microenvironment.

We welcome a variety of article types, including under the following categories: Original Research, Review, Mini Review, Brief Research Report, and Perspective.

Keywords: Ovarian Cancer, PARP Resistance, Ovarian Tumors, PARP Inhibitors, Immunotherapy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.