Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland.
Department of Clinical Immunology, St. John's Cancer Centre, 7 Jaczewskiego Street, 20-090 Lublin, Poland.
Int J Mol Sci. 2019 Sep 23;20(19):4705. doi: 10.3390/ijms20194705.
Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.
尽管癌症研究不断取得进展，但全球癌症负担在 2018 年已增加到 1810 万例新发病例和 960 万死亡病例。妇科癌症，如卵巢癌、子宫内膜癌和宫颈癌，对全球癌症负担有很大贡献，分别导致每年癌症治疗费用为 58.626 亿美元、29.457 亿美元和 15.439 亿美元。因此，开发针对妇科癌症的有效治疗方法仍然是一个尚未满足的医学需求。一种新的治疗方法是通过使用单克隆抗体抑制免疫检查点途径来诱导抗癌免疫。单克隆抗体的分子靶标是细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）、程序性细胞死亡蛋白 1（PD-1）和程序性死亡配体 1（PD-L1）。在妇科癌症患者中使用免疫检查点抑制剂的依据是免疫组织化学研究显示这些癌症中 PD-1 和 PD-L1 的高表达水平。目前可用的免疫检查点抑制剂包括纳武单抗、帕博利珠单抗、阿特珠单抗、avelumab、度伐鲁单抗和伊匹单抗。这些抑制剂作为单药治疗以及与化疗联合使用的疗效和安全性正在几项临床研究中进行评估。由于结果很有前景，正在计划更多的临床试验，这可能会为妇科癌症患者开发出有效的治疗方法。
