Molecular Signaling Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Ann Oncol. 2010 Oct;21 Suppl 7(Suppl 7):vii205-10. doi: 10.1093/annonc/mdq375.
Ovarian cancer remains the deadliest gynecological malignancy in the Western world and is most often diagnosed at a rarely curable late stage. Examination of protein end points has been employed as an investigative mechanism to guide targeted therapy and to stratify ovarian cancer. Proteomics allows characterization of the proteins and the associated protein and peptide modifications. This has given us insight into the perturbations of signaling pathways within tumor cells and has improved the discovery of new drug targets and possible prognostic indicators of outcome and disease response to therapy. Development of validated assays that survey the genetic and/or proteomic make-up of an individual tumor will add greatly to the histological classification of the tumor and may lead to different treatment approaches tailored to the unique expression pattern of each individual patient. It is anticipated that application of proteomics may bring to reality the clinical adoption of molecular stratification, e.g. not, 'is the gene overexpressed?', but 'is the pathway upregulated?' This will be successful if validated peptide biomarkers are applied for patient selection prospectively and with inclusion of preplanned biological correlates. These events will guide future directions of proteomics as a selector and as a validator and will guide how we integrate proteomics information daily into patient care and into selecting therapy of advanced and recurrent ovarian cancer and other cancers.
卵巢癌仍然是西方世界最致命的妇科恶性肿瘤,大多数情况下在难以治愈的晚期被诊断出来。蛋白终点的检查被用作一种研究机制,以指导靶向治疗和对卵巢癌进行分层。蛋白质组学允许对蛋白质以及相关的蛋白质和肽修饰进行描述。这使我们深入了解了肿瘤细胞内信号通路的紊乱,并提高了对新药物靶点的发现,以及对预后和疾病对治疗反应的可能预测指标的认识。开发经过验证的检测方法来检测个体肿瘤的遗传和/或蛋白质组学组成,将极大地增加肿瘤的组织学分类,并可能导致针对每个个体患者独特表达模式的不同治疗方法。预计蛋白质组学的应用将使分子分层的临床应用成为现实,例如,不是“基因是否过表达?”,而是“途径是否上调?”如果前瞻性地应用验证过的肽生物标志物进行患者选择,并包括预先计划的生物学相关性,这将是成功的。这些事件将指导蛋白质组学作为选择器和验证器的未来方向,并指导我们如何将蛋白质组学信息整合到日常的患者护理中,以及如何选择晚期和复发性卵巢癌和其他癌症的治疗方法。