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Optimizing Molecular-Targeted Therapies in Ovarian Cancer: The Renewed Surge of Interest in Ovarian Cancer Biomarkers and Cell Signaling Pathways

机译:在卵巢癌中优化分子靶向治疗:卵巢癌生物标志物和细胞信号通路的兴趣重新兴起

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The hallmarks of ovarian cancer encompass the development of resistance, disease recurrence and poor prognosis. Ovarian cancer cells express gene signatures which pose significant challenges for cancer drug development, therapeutics, prevention and management. Despite enhancements in contemporary tumor debulking surgery, tentative combination regimens and abdominal radiation which can achieve beneficial response rates, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapse. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free and overall response rates in ovarian cancer patients. Currently, a revival in cancer drug discovery is devoted to identifying diagnostic and prognostic ovarian cancer biomarkers. However, the sensitivity and reliability of such biomarkers may be complicated by mutations in theBRCA1orBRCA2genes, diverse genetic risk factors, unidentified initiation and progression elements, molecular tumor heterogeneity and disease staging. There is thus a dire need to expand existing ovarian cancer therapies with broad-spectrum and individualized molecular targeted approaches. The aim of this review is to profile recent developments in our understanding of the interrelationships among selected ovarian tumor biomarkers, heterogeneous expression signatures and related molecular signal transduction pathways, and their translation into more efficacious targeted treatment rationales.
机译:卵巢癌的标志性疾病包括耐药性的发展,疾病的复发和不良预后。卵巢癌细胞表达基因签名,这对癌症药物的开发,治疗,预防和管理提出了重大挑战。尽管现代肿瘤切除术,试验性联合治疗方案和腹部放疗可以达到有益的应答率,但大多数卵巢癌患者不仅会出现不良反应,而且最终会复发。因此,需要探索其他治疗可能性,以最大程度地减少卵巢癌患者的不良事件并延长无进展和总体缓解率。当前,癌症药物发现的复兴致力于鉴定诊断性和预后性卵巢癌生物标志物。然而,此类生物标志物的敏感性和可靠性可能因BRCA1或BRCA2基因的突变,多种遗传危险因素,不确定的起始和进展成分,分子肿瘤异质性和疾病分期而变得复杂。因此,迫切需要使用广谱和个性化的分子靶向方法来扩展现有的卵巢癌治疗方法。这篇综述的目的是概述我们对所选卵巢肿瘤生物标志物,异种表达特征和相关分子信号转导途径之间的相互关系的理解的最新进展,以及将它们翻译成更有效的靶向治疗原理的过程。

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