Gregory Lee, Cheng-yuan Huang and Bixia Ge
Two monoclonal antibodies (Mab) were selected for development of anti-cancer drugs targeting ovarian cancer. RP215 Mab was shown to react with a carbohydrate-associated epitope detected mainly in the heavy chains of cancer cell-expressed immunoglobulins which are essential for the growth/proliferation of almost all human cancer cells. GHR106 Mab, on the other hand, reacts specifically with GnRH receptor on the surface of almost all cancer cells. In this review, efforts were made to use an ovarian cancer cell line, OC-3-VGH as the experimental model to study these two Mabs in murine and humanized isoforms including humanization, comparative biochemical and immunological characterizations. Surface binding of either of these two Mabs can result in apoptosis and complement-dependent cellular cytotoxicity to this ovarian cancer cell line and others. Both murine Mabs were humanized and shown to be bioequivalent with respect to affinity and biospecificity to their murine counterparts through extensive biochemical/immunological studies. Therefore, preclinical and clinical studies were warranted to continue the investigations of these two potential anti-cancer drug candidates for therapeutic treatments of ovarian cancer.
Toss A and Cortesi L
Ovarian cancer continues to be the main cause of death among all gynecological tumors. After standard treatments, most of patients are destined to recur within a short period, thus new therapies are urgently needed. The increasing knowledge of molecular mechanisms in ovarian cancer pathogenesis allowed identifying several targeted agents that are now entering in clinical practice. The family of poly(ADP-ribose) polymerase inhibitors represents a widely investigated and promising alternative for the targeted therapy of ovarian malignancies. PARP inhibitors exploit the synthetic lethality concept to prevent the repair of DNA damage, causing cancer cell death. This review describes the molecular mechanisms at the basis of PARP inhibition, particularly in BRCA-related ovarian malignancies and analyzes the main agents under investigations in preclinical and clinical studies.