Current Ovarian Cancer Maintenance Strategies and Promising New Developments

Abstract

While ovarian cancer typically responds well to front line treatment, many patients will relapse within 5 years. Treatment options are less effective at each recurrence highlighting the need for novel maintenance therapies. PolyADP-ribose polymerase (PARP) inhibitors have recently gained approval in ovarian cancer maintenance. Niraparib was approved regardless of BRCA mutation status, however impact on overall survival is limited. Oliparib was approved for BRCA mutant and BRCA wildtype/homologous recombination deficient patients. This review will focus on current frontline ovarian cancer treatment as well molecularly based approaches to ovarian cancer management.

Keywords: HGSOC; Vigil; ovarian cancer maintenance; ovarian cancer treatment.

Figure 1

Currently approved therapies in ovarian cancer maintenance. Platinum therapies function by damaging DNA through the formation of cross-links. PARP inhibitors function by disrupting PARP, a key molecule in the DNA repair complex. This kills tumorous cells by the principle of synthetic lethality in homologous repair deficient patients, such as BRCA-mutant. Taxanes prevent depolymerization of microtubules, thereby disrupting the mitotic spindle's ability to separate in mitosis. Angiogenesis inhibitors interrupt the interaction of proangiogenic factors with their receptors, effectively halting angiogenesis in the tumor microenvironment.

Figure 2

Ovarian cancer therapeutics under investigation. Many of these therapeutics interact with components of the immune system. Vigil is an autologous vaccine that introduces neoantigens and enhances function of T cells to select for those antigens (A). Sotio DVAC introduces neoantigens directly into nondifferentiated antigen presenting cells, which the mount them on MHC (B). Peptide based approaches introduce neoantigens into the serum, which are recognized by antigen presenting cells and mounted on to MHC (C). CAR-T based therapy introduces known antigen receptors directly onto T-cells (D). Immune checkpoint inhibitors inhibit the immunoregulatory signal between T cells and cancer cells (E). Viral therapies are used to alter gene expression on tumor cells (F). CA-125 antibody binds the receptor which induces an immune response (G).