Kathawala Rishil J, Kudelka Andrzej, Rigas Basil
Department of Medicine, Stony Brook University, Stony Brook, NY USA.
Curr Pharmacol Rep. 2018;4(3):250-260. doi: 10.1007/s40495-018-0133-6. Epub 2018 May 2.
Ovarian 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.
OvCa chemoprevention represents an opportunity for all women, especially those at high risk such as carriers of or 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.
Currently, 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.
卵巢癌是所有妇科癌症中致死率最高的，5年生存率约为46%，主要原因是早期诊断和治疗存在局限性。因此，卵巢癌的化学预防成为控制这种严重疾病的重要选择。在此，我们讨论风险评估在卵巢癌化学预防策略设计中的作用，描述候选药物，并评估该领域的未来方向。
卵巢癌化学预防对所有女性来说都是一个机会，尤其是那些高危人群，如携带特定基因突变的女性。口服避孕药对卵巢癌具有显著的预防作用，包括高危女性，服用时间越长预防效果越好。尽管有充分证据证明其有效性，但安全问题以及所需干预性临床试验的规模似乎阻碍了对口服避孕药用于此用途的确定性研究。其他几类药物，包括非甾体抗炎药、维甲酸、血管预防剂、聚（ADP - 核糖）聚合酶抑制剂和酪氨酸激酶抑制剂，在卵巢癌化学预防方面已显示出前景。
目前，尚无干预性试验证明任何药物具有预防卵巢癌的化学预防特性。卵巢癌化学预防的关键机遇包括开发卵巢癌的替代生物标志物、明确卵巢癌风险的分子定义以帮助选择可能从化学预防中获益最大的人群、通过了解卵巢癌的分子发病机制确定其他可能的药物，以及为卵巢癌开发专门的资源和支持机制。总体而言，卵巢癌化学预防的未来前景十分乐观。
