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本文引用的文献

1
Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia.贝伐单抗与低剂量节拍口服环磷酰胺治疗复发性卵巢癌的II期临床试验:加利福尼亚、芝加哥和玛格丽特公主医院II期联合研究组的一项试验
J Clin Oncol. 2008 Jan 1;26(1):76-82. doi: 10.1200/JCO.2007.12.1939.
2
Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study.贝伐单抗用于持续性或复发性上皮性卵巢癌或原发性腹膜癌的II期试验:一项妇科肿瘤学组研究
J Clin Oncol. 2007 Nov 20;25(33):5165-71. doi: 10.1200/JCO.2007.11.5345.
3
Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma.蛋白激酶C(PKC)家族的综合基因组分析确定PKCiota为卵巢癌的生物标志物和潜在致癌基因。
Cancer Res. 2006 May 1;66(9):4627-35. doi: 10.1158/0008-5472.CAN-05-4527.
4
Chaperoning oncogenes: Hsp90 as a target of geldanamycin.陪伴癌基因:热休克蛋白90作为格尔德霉素的作用靶点。
Handb Exp Pharmacol. 2006(172):259-77. doi: 10.1007/3-540-29717-0_11.
5
Cyclin-dependent kinase pathways as targets for cancer treatment.细胞周期蛋白依赖性激酶通路作为癌症治疗的靶点。
J Clin Oncol. 2006 Apr 10;24(11):1770-83. doi: 10.1200/JCO.2005.03.7689.
6
Angiogenesis and cancer: A cross-talk between basic science and clinical trials (the "do ut des" paradigm).
Crit Rev Oncol Hematol. 2006 Jul;59(1):40-50. doi: 10.1016/j.critrevonc.2006.02.007. Epub 2006 Apr 4.
7
Epidermal growth factor receptor inhibitors in cancer treatment.癌症治疗中的表皮生长因子受体抑制剂
Future Oncol. 2005 Apr;1(2):221-34. doi: 10.1517/14796694.1.2.221.
8
Epithelial growth factor receptor status in primary and recurrent ovarian cancer.原发性和复发性卵巢癌中的表皮生长因子受体状态
Mod Pathol. 2006 Apr;19(4):607-10. doi: 10.1038/modpathol.3800575.
9
The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer.基质金属蛋白酶在卵巢癌中的表达的临床相关性。
Clin Cancer Res. 2006 Mar 15;12(6):1707-14. doi: 10.1158/1078-0432.CCR-05-2338.
10
Akt-mediated cisplatin resistance in ovarian cancer: modulation of p53 action on caspase-dependent mitochondrial death pathway.Akt介导的卵巢癌顺铂耐药:p53对依赖半胱天冬酶的线粒体死亡途径作用的调节
Cancer Res. 2006 Mar 15;66(6):3126-36. doi: 10.1158/0008-5472.CAN-05-0425.

相关分子标志物与靶点。

Relevant molecular markers and targets.

作者信息

Darcy Kathleen M, Schilder Russel J

机构信息

Translational Research Scientist, Gynecologic Oncology Group, Statistical and Data Center, Roswell Park Cancer Institute, Research Studies Center, Rm. 516, Carlton and Elm Streets, Buffalo, NY 14263, USA.

出版信息

Gynecol Oncol. 2006 Nov;103(2 Suppl 1):S6-S13. doi: 10.1016/j.ygyno.2006.08.018. Epub 2006 Oct 10.

DOI:10.1016/j.ygyno.2006.08.018
PMID:17034839
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1868014/
Abstract

Ovarian cancer is a heterogeneous disease with extensive cytogenetic and molecular heterogeneity including aneuploidy, chromosomal alterations, mutations and overexpression as well as a natural propensity to disseminate and spread, making it difficult to diagnose at an early stage. Insights into the molecular mechanisms operative in cancer development, progression and metastasis have uncovered a wide array of targets for therapeutic intervention. In the absence of a common driving oncogene in ovarian cancer, single targeted therapy for this disease is unlikely to yield significant clinical benefit. Tailored approaches that combine molecular targeting agents with cytotoxic regimens hold great promise when used in primary treatment, during consolidation and maintenance therapy, and in the treatment of persistent or recurrent disease. The most promising treatment strategies are those that target the drivers of tumorigenesis and enhance the activity of cytotoxic agents. Receptor tyrosine kinases, non-receptor tyrosine kinases, serine/threonine kinases, transferases, proteases and deacetylases are among the relevant molecular markers and targets for ovarian cancer that are discussed. Collaboration, coordination, creativity and aggressive outreach to patients and their advocates are essential for success in running the concurrent trials with multiple clinical end points and embedded translational research that are needed to evaluate the array of promising targeted therapeutics and combinations. Validated biomarkers, surrogate specimens and end points, and additional clinically relevant in vitro and in vivo models for ovarian cancer are needed to facilitate the drug development and evaluation process, and ultimately to make meaningful improvements in the diagnosis, prevention and management of ovarian cancer.

摘要

卵巢癌是一种异质性疾病,具有广泛的细胞遗传学和分子异质性,包括非整倍体、染色体改变、突变和过表达,以及自然的播散和扩散倾向,这使得早期诊断变得困难。对癌症发生、发展和转移过程中起作用的分子机制的深入了解揭示了大量可供治疗干预的靶点。由于卵巢癌中不存在共同的驱动癌基因,针对这种疾病的单一靶向治疗不太可能产生显著的临床益处。将分子靶向药物与细胞毒性方案相结合的定制方法在用于一线治疗、巩固和维持治疗以及持续性或复发性疾病的治疗时具有很大的前景。最有前景的治疗策略是那些针对肿瘤发生驱动因素并增强细胞毒性药物活性的策略。受体酪氨酸激酶、非受体酪氨酸激酶、丝氨酸/苏氨酸激酶、转移酶、蛋白酶和脱乙酰酶是本文讨论的卵巢癌相关分子标志物和靶点。对于开展具有多个临床终点并嵌入转化研究的同步试验以评估一系列有前景的靶向治疗药物及其联合用药而言,合作、协调、创造力以及积极与患者及其支持者沟通至关重要。需要经过验证的生物标志物、替代标本和终点,以及其他与卵巢癌临床相关的体外和体内模型,以促进药物开发和评估过程,并最终在卵巢癌的诊断、预防和管理方面取得有意义的进展。