摘要
正常细胞必须克服多种保护机制才能发展为癌细胞。它们的新功能包括生长信号的自给和对抗生长信号的不敏感性,细胞凋亡的逃避,无限的复制潜力,持续的血管生成以及组织的侵袭和转移。这些也被称为癌症的六个标志。对这些过程中涉及的遗传和蛋白质改变的深入了解,使得寻找卵巢癌治疗方法的靶向治疗策略和临床试验设计得以发展。临床上,单用PARP,MEK,VEGF和Chk1 / Chk2抑制剂可观察到更长的无进展生存期。但是,靶向药物的临床疗效仍仅限于特定的分子亚型,尚无试验表明总生存获益。探索新的药物靶标或结合当前可行的生物制剂,有望进一步改善卵巢癌的治疗效果。在这篇综述中,我们打算对涉及卵巢癌致癌作用的分子变化和新兴生物因子以及针对异常途径的联合策略进行全面描述,这可能为将来的卵巢癌治疗提供启示。
关键词: 卵巢癌,癌症标志,靶向治疗,PARP,MEK,VEGF。
图形摘要
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1002/14651858.CD007929.pub3] [PMID: 25991068]
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID: 30345884]
[http://dx.doi.org/10.1016/S0092-8674(00)81683-9] [PMID: 10647931]
[http://dx.doi.org/10.1200/JCO.2006.07.9970] [PMID: 18195328]
[http://dx.doi.org/10.1155/2010/414676] [PMID: 20066160]
[http://dx.doi.org/10.1016/j.cell.2007.05.018] [PMID: 17540168]
[http://dx.doi.org/10.1016/0092-8674(90)90018-A] [PMID: 2199064]
[http://dx.doi.org/10.3390/cancers11081182] [PMID: 31443240]
[http://dx.doi.org/10.3389/fphar.2015.00283] [PMID: 26635612]
[http://dx.doi.org/10.3390/ijms20194693] [PMID: 31546690]
[http://dx.doi.org/10.1002/14651858.CD007927.pub3] [PMID: 21975775]
[http://dx.doi.org/10.1016/j.ajps.2019.06.001] [PMID: 32175016]
[http://dx.doi.org/10.1016/j.colsurfb.2019.03.011] [PMID: 30856589]
[http://dx.doi.org/10.2174/1872210513666181128162403] [PMID: 30488805]
[http://dx.doi.org/10.2147/DDDT.S82035] [PMID: 26124641]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2662]
[http://dx.doi.org/10.1111/joim.13057] [PMID: 32176377]
[http://dx.doi.org/10.1016/j.apsb.2019.03.002] [PMID: 31649840]
[http://dx.doi.org/10.1016/j.ygyno.2014.02.017] [PMID: 24556063]
[http://dx.doi.org/10.1016/j.ygyno.2011.06.022] [PMID: 21752435]
[http://dx.doi.org/10.1016/j.ctrv.2014.12.003] [PMID: 25573350]
[http://dx.doi.org/10.1056/NEJMoa1502309] [PMID: 26287849]
[http://dx.doi.org/10.1016/S1470-2045(12)70572-7] [PMID: 23261356]
[http://dx.doi.org/10.1016/j.ygyno.2019.12.002] [PMID: 31870556]
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0240] [PMID: 21632463]
[http://dx.doi.org/10.1007/s11523-017-0530-5] [PMID: 29067643]
[http://dx.doi.org/10.1073/pnas.1904529116] [PMID: 31332011]
[http://dx.doi.org/10.1038/s41586-019-1694-1] [PMID: 31666701]
[http://dx.doi.org/10.1016/j.ctrv.2020.101974] [PMID: 32014824]
[http://dx.doi.org/10.1101/cshperspect.a026104] [PMID: 26931810]
[PMID: 8700537]
[http://dx.doi.org/10.1016/j.tcb.2015.04.001] [PMID: 25960041]
[http://dx.doi.org/10.1158/2159-8290.CD-16-0860] [PMID: 28003236]
[http://dx.doi.org/10.1007/s40273-018-0745-z] [PMID: 30478649]
[http://dx.doi.org/10.1056/NEJMoa1611310] [PMID: 27717299]
[http://dx.doi.org/10.1016/S1470-2045(17)30469-2] [PMID: 28754483]
[http://dx.doi.org/10.1016/S1470-2045(16)30559-9] [PMID: 27908594]
[http://dx.doi.org/10.1016/S1470-2045(14)70228-1] [PMID: 24882434]
[http://dx.doi.org/10.1016/S1470-2045(14)71135-0] [PMID: 25481791]
[http://dx.doi.org/10.1056/NEJMoa1910962] [PMID: 31562799]
[http://dx.doi.org/10.1056/NEJMoa1909707] [PMID: 31562800]
[http://dx.doi.org/10.1200/JCO.2017.76.6915] [PMID: 29252124]
[http://dx.doi.org/10.1016/j.pharmthera.2019.107450] [PMID: 31836456]
[http://dx.doi.org/10.1016/S1470-2045(18)30009-3] [PMID: 29361470]
[http://dx.doi.org/10.1080/13543784.2019.1657403] [PMID: 31449760]
[http://dx.doi.org/10.1016/j.ccr.2006.11.024] [PMID: 17292828]
[http://dx.doi.org/10.1016/j.molcel.2010.09.018] [PMID: 20932473]
[http://dx.doi.org/10.1016/j.celrep.2013.10.025] [PMID: 24239348]
[http://dx.doi.org/10.3390/cancers12030654] [PMID: 32168910]
[http://dx.doi.org/10.4049/jimmunol.177.8.5668] [PMID: 17015756]
[http://dx.doi.org/10.1007/s12032-018-1131-6] [PMID: 29651744]
[http://dx.doi.org/10.1200/JCO.2016.34.15_suppl.5511]
[http://dx.doi.org/10.1002/cncr.32520] [PMID: 31967676]
[http://dx.doi.org/10.1016/j.trecan.2019.06.004] [PMID: 31474356]
[http://dx.doi.org/10.1016/j.celrep.2018.11.054] [PMID: 30540933]
[http://dx.doi.org/10.1001/jamaoncol.2019.1048] [PMID: 31194228]
[http://dx.doi.org/10.1016/S0140-6736(20)30165-3] [PMID: 32145796]
[http://dx.doi.org/10.1016/j.ebiom.2019.04.009] [PMID: 30979685]
[http://dx.doi.org/10.1080/14728214.2019.1696773] [PMID: 31755325]
[http://dx.doi.org/10.1200/JCO.2014.60.4009] [PMID: 25964244]
[http://dx.doi.org/10.3109/07357900802491451] [PMID: 19909010]
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0056] [PMID: 19671744]
[http://dx.doi.org/10.1038/cgt.2009.44] [PMID: 19662088]
[http://dx.doi.org/10.1056/NEJMoa1104390] [PMID: 22204724]
[http://dx.doi.org/10.1056/NEJMoa1103799] [PMID: 22204725]
[http://dx.doi.org/10.1200/JCO.2012.42.0505] [PMID: 22529265]
[http://dx.doi.org/10.1200/JCO.2013.51.4489] [PMID: 24637997]
[http://dx.doi.org/10.1200/JCO.2014.55.7348] [PMID: 25225436]
[http://dx.doi.org/10.1016/S1470-2045(15)00366-6] [PMID: 26590673]
[http://dx.doi.org/10.1200/JCO.2010.33.5208] [PMID: 21859991]
[http://dx.doi.org/10.1016/S0140-6736(15)01167-8] [PMID: 27025186]
[http://dx.doi.org/10.1016/S1470-2045(15)70115-4] [PMID: 25882986]
[http://dx.doi.org/10.1016/j.ygyno.2013.04.011] [PMID: 23591401]
[http://dx.doi.org/10.1016/S1470-2045(14)70244-X] [PMID: 24950985]
[http://dx.doi.org/10.1200/JCO.2010.34.3178] [PMID: 22184370]
[http://dx.doi.org/10.1185/03007995.2015.1131152] [PMID: 26652645]
[http://dx.doi.org/10.7573/dic.212558] [PMID: 30627206]
[http://dx.doi.org/10.1056/NEJMoa1911361] [PMID: 31851799]
[http://dx.doi.org/10.1016/S0896-6273(00)80276-7] [PMID: 8755474]
[http://dx.doi.org/10.1093/jnci/djj414] [PMID: 17077358]
[http://dx.doi.org/10.1517/14728222.9.6.1179] [PMID: 16300469]
[http://dx.doi.org/10.1200/JCO.2008.18.1107] [PMID: 18854563]
[http://dx.doi.org/10.3390/cancers9070083] [PMID: 28698469]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5167] [PMID: 18381440]
[http://dx.doi.org/10.1016/j.ygyno.2010.12.362] [PMID: 21276608]
[http://dx.doi.org/10.4161/cbt.28882] [PMID: 24755674]
[http://dx.doi.org/10.1021/jm800483v] [PMID: 18989950]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2667] [PMID: 18006843]
[http://dx.doi.org/10.4161/cbt.8.11.8523] [PMID: 19395869]