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Multifaceted and personalized therapy of advanced prostate cancer

机译:晚期前列腺癌的多方面和个性化治疗

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摘要

Purpose of reviewA number of molecular and genomic biomarkers that possess the ability to guide treatment or actionable targets' are being reported in metastatic prostate cancer. In addition, pathways of resistance to existing therapies and novel agents to overcome them are currently under active investigation. The next wave of investigations is focused on personalized therapy of prostate cancer. The focus of this review article is to provide an update on clinical development in advanced prostate cancer and to highlight the ongoing investigations of biomarker discovery, and ways of overcoming therapeutic resistance. The next generation of clinical trials developing novel targets and compounds promises to be in populations enriched with specific marker expression.Recent findingsThe breakthrough report, of the ability of the androgen receptor variant 7 mutation, detected in circulating tumor cells, to predict the lack of response to abiraterone or enzalutamide, and the remarkable responses of poly adenosine diphosphate ribose polymerase inhibitors in prostate cancer with DNA repair mutations have elevated hopes of a bright future in the biomarker-driven therapeutic arena. Novel targets such as bromodomain extra terminal-1 and phosphatidylinositol 3-kinase hold promise for the possibility of overcoming resistance. Novel hormone agents are also under active study.SummaryAs the clinical application of the multifaceted therapies narrows down to enriched patient populations selected by genomic testing, the therapeutic efficiency will escalate considerably. Novel targets, resistance mechanisms and relevant agents are being avidly tested, and the dream of personalized medicine is emerging into reality.
机译:综述的目的在转移性前列腺癌中报告了许多具有指导治疗或可操作靶标的能力的分子和基因组生物标志物。此外,目前正在积极研究对现有疗法和新药的耐药性途径。下一波研究集中在前列腺癌的个性化治疗上。本文的重点是提供有关晚期前列腺癌临床发展的最新信息,并强调正在进行的生物标志物发现研究以及克服治疗耐药性的方法。开发新型靶标和化合物的下一代临床试验有望出现在富含特异性标志物表达的人群中。最新发现突破性报告报道了在循环肿瘤细胞中检测到的雄激素受体变异体7突变的能力,以预测缺乏反应对于阿比特龙或恩杂鲁胺,聚腺苷二磷酸核糖聚合酶抑制剂在具有DNA修复突变的前列腺癌中的显着反应,增加了在生物标记物驱动的治疗领域中光明前景的希望。诸如溴结构域额外末端1和磷脂酰肌醇3-激酶等新型靶标有望克服耐药性。新型激素药物也正在积极研究中。总结随着多方面疗法的临床应用缩小到通过基因组测试选择的丰富患者人群,治疗效率将大大提高。新型靶标,耐药机制和相关药物正在受到热烈的测试,个性化医学的梦想正在变为现实。

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