Weberpals Johanne I, Koti Madhuri, Squire Jeremy A
Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Cancer Genet. 2011 Oct;204(10):525-35. doi: 10.1016/j.cancergen.2011.09.004.
Genomic information is being used to develop robust prognostic and predictive biomarkers that will provide companion diagnostics for emerging molecular targeted therapies. The genetics and associated molecular pathways in ovarian cancer are increasingly being used for the development of novel targeted drugs with a much greater therapeutic specificity than standard chemotherapy. This review will provide an update on recent research on the therapeutic opportunities presented by mutational alterations to the epidermal growth factor receptor (EGFR) and phosphatidylinositide-3-kinase (PI3K/AKT/mTOR) pathways. In addition, the role of the deficient BRCA1/2-mediated homologous recombination (HR) ("BRCAness") pathway is presented. Understanding the molecular biology of these pathways in the context of contemporary drug development means that somatic mutations and epigenetic losses of BRCA1/2 and PTEN in ovarian cancer are being used to predict sensitivity to new poly(ADP-ribose) polymerase (PARP) inhibitors that exhibit synthetic lethality with BRCA1/2 dysfunction and other repair pathways. Future predictive "biomarker pipelines" are being developed so that ovarian cancer patients will be able to avoid having treatments with drugs that will have no effect, whereas other patients with cancer may be eligible for therapies with a much higher probability of treatment response.
基因组信息正被用于开发强大的预后和预测生物标志物，这些生物标志物将为新兴的分子靶向疗法提供伴随诊断。卵巢癌的遗传学及相关分子途径越来越多地被用于开发新型靶向药物，其治疗特异性比标准化疗高得多。本综述将更新关于表皮生长因子受体（EGFR）和磷脂酰肌醇-3-激酶（PI3K/AKT/mTOR）途径突变改变所带来的治疗机会的近期研究。此外，还介绍了缺陷的BRCA1/2介导的同源重组（HR）（“BRCAness”）途径的作用。在当代药物开发背景下理解这些途径的分子生物学意味着，卵巢癌中BRCA1/2和PTEN的体细胞突变和表观遗传缺失正被用于预测对新的聚（ADP-核糖）聚合酶（PARP）抑制剂的敏感性，这些抑制剂与BRCA1/2功能障碍及其他修复途径表现出合成致死性。未来正在开发预测性“生物标志物管道”，以便卵巢癌患者能够避免使用无效的药物进行治疗，而其他癌症患者可能有资格接受治疗反应概率更高的疗法。
