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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.

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。

相似文献

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Relevant molecular markers and targets.相关分子标志物与靶点。
Gynecol Oncol. 2006 Nov;103(2 Suppl 1):S6-S13. doi: 10.1016/j.ygyno.2006.08.018. Epub 2006 Oct 10.

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