A Current Review of Targeted Therapeutics for Ovarian Cancer

Abstract

Difficult to detect, ovarian cancer typically presents at an advanced stage. Significant progress has been achieved in the treatment of ovarian cancer with therapeutics focused on DNA replication or cell division. However, despite sensitivity to induction chemotherapy the majority of patients will develop recurrent disease. Conventional agents for recurrent disease offer little in terms of long-term responses. Various targeted therapeutics have been explored in the management of ovarian cancer. These include monoclonal antibodies to epidermal growth factor receptors, small molecule tyrosine kinase inhibitors, monoclonal antibodies directed at the vascular endothelial growth factor (bevacizumab), and the small tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor. Recently, several other agents have come forth as potential therapeutic agents in the management of ovarian cancer. These include monoclonal antibodies to the folate receptor, triple angiokinase inhibitors, PARP inhibitors, aurora kinase inhibitors, inhibitors of the Hedgehog pathway, folate receptor antagonists, and MTOR inhibitors.

Serous ovarian carcinoma. Cytological and immunocytochemical and molecular genetic diagnostics

“…Около 80 % случаев РЯ диагностируют на III-IV стадиях болезни. Опухолевый метастатический асцит и плеврит -частые осложнения при РЯ, летальный исход при РЯ в основном связан с распространением метастазов по перитонеальным и / или плевральным поверхностям [16,17]. Исследование асцитической и плевральной жидкости в алгоритме обследования пациенток занимает важное место.…”

Targeted Agents in Ovarian Carcinoma

“…5-10% of ovarian carcinoma patients have a mutation in BRCA-1 and BRCA-2 gene; the lifetime risk of developing ovarian cancer for this gene mutation carriers is 40-50% and 10-20% respectively [50]. Olaparib, Niraparib and Rucaparib are examples of these drugs.…”

“…There are three aurora kinases as A, B and C which take an active role during the G2-M phase of the cell cyle [50]. Aurora-A is especially important for centrosome functions [57] and Aurora-A is a potential oncogene [58] whose polymorphisms are related with 18-25% increased risk of ovarian cancer additionally breast or colon cancer [59,60].…”

“…Landen et al [61] checked Aurora-A staining in ovarian cancer tissues after primary cytoreductive surgery and they found 82.9% of cases were having a staining greater than normal epithelium. Moreover Aurora kinase A overexpression is significantly associated with tumor grade, FIGO stage and survival [50].…”

Epithelial Ovarian Cancer

“…Further, a number of recent studies have indicated that EOC is linked to aberrant cell signaling, including Hedgehog (Hh) and platelet-derived growth factor (PDGF) signaling as well as over-expression of aurora A kinase (AURA) and deregulated expression of the novel tumor suppressor protein, checkpoint with forkhead-associated and ring finger domains (CHFR) [7][8][9][10][11][12][13][14][15][16][17][18][19]. Consequently, targeted agents against Hh pathway components, PDGFR and AURA have been explored recently in the management of ovarian cancer and recurrent disease [20].…”