The Chemoprevention of Ovarian Cancer: the Need and the Options

Abstract

Purpose of ReviewOvarian cancer (OvCa) is the most lethal of all gynecological cancers, with a 5-year survival around 46%, mainly due to limitations in early diagnosis and treatment. Consequently, the chemoprevention of OvCa emerges as an important option to control this dismal disease. Here, we discuss the role of risk assessment in the design of chemoprevention strategies for OvCa, describe candidate agents, and assess future directions in this field.Recent FindingsOvCa chemoprevention represents an opportunity for all women, especially those at high risk such as carriers of BRCA1 or BRCA2 mutations. The use of oral contraceptives confers substantial protection against OvCa including women at high risk, which increases with longer use. Despite strong evidence for their efficacy, safety concerns and the magnitude of the requisite interventional clinical trials seem to have precluded definitive studies of oral contraceptives for this application. Several other classes of drugs, including non-steroidal anti-inflammatory drugs, retinoids, angiopreventive agents, poly(ADP-ribose) polymerase inhibitors, and tyrosine kinase inhibitors have shown promise for OvCa chemoprevention.SummaryCurrently, no agent is proven by interventional trials to possess chemopreventive properties against OvCa. The key opportunities in the chemoprevention of OvCa include the development of surrogate biomarkers for OvCa, the molecular definition of OvCa risk that will help select those who may benefit the most from chemoprevention, the identification of additional agents likely driven by understanding the molecular pathogenesis of OvCa, and the development of dedicated resources and support mechanisms for OvCa. Overall, there is significant optimism for the future of OvCa chemoprevention.

Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue—Going Beyond Apoptosis Induction

“…Master modifiers may intervene in communication-driven homeostatic processes between epithelial/mesenchymal/hematologic cells and adjacent stroma cells for preventing the formation of possible tumor initiating niches (169). Peroxisome proliferator-activated receptor gamma and retinoids have already shown in animal models chemopreventive effects (80,170,171). It is suggested, that pharmacological interventions are capable of altering precancerous niches, thus potentially reducing the cancer risk in individuals with germline mutations (168).…”

PARP-inhibitors in epithelial ovarian cancer: Actual positioning and future expectations

“…To date, prophylactic salpingo-oophorectomy is recommended at 40-45 years old for germline mBRCA carriers, which do not preclude earlier onset and generates complications of precocious estrogen lack. Currently, no agent showed chemo-preventive properties against HGOC in interventional trials [66]. As PARPi had relevant toxicity and is expensive, it is unlikely that they will play a relevant role in this setting.…”

Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia

“…1 Chemoprevention holds promise but remains an understudied paradigm to reduce ovarian cancer burden. 2 Chronic inflammation likely plays a key role in ovarian carcinogenesis, 3 as factors associated with epithelial disruption from ovulation, 4,5 inflammation-related exposures such as endometriosis and pelvic inflammatory disease, 6,7 and circulating biomarkers of inflammation 8,9 are associated with ovarian cancer risk. Anti-inflammatory medications such as aspirin may lower risk of ovarian cancer development via inhibition of the cyclooxygenase enzymes, leading to decreased synthesis of inflammatory mediators, or via cyclooxygenase-independent pathways including inhibition of Wnt/b-catenin and NF-kb.…”

“…2 = 0.02, I 2 = 42.84%, H 2 = 1.75 Heterogeneity: W 2 = 0.00, I 2 = 0.00%, H 2 = 1.00 Heterogeneity: W 2 = 0.00, I 2 = 10.66%, H 2 = 1.12 Test of T i = T j : Q(7) = 12.21, P = .09 Test of T i = T j : Q(8) = 4.02, P = .85 Test of T i = T j : Q(16) = 17.28, P = .37 Test of group differences: Q b (1) = 0.51, P = .…”