Kondo Tadashi
Division of Pharmacoproteomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Rinsho Byori. 2012 Jul;60(7):644-9.
Cancer is a genetically and clinically diverse disease, and the therapeutic strategies should be optimized for individual cases. Recent advances in pharmacogenomics have generated molecular targeting anti-cancer drugs, and their optimized uses are an emergent challenge. Biomarkers are key tools to assess the malignant potential of tumor cells and to establish risk-stratified therapies. The proteome is a functional translation of the genome and it directly regulates the malignant phenotypes of tumor cells; thus, a proteomic approach could make significant contributions to biomarker development. In the past decade, proteomics technologies have progressed extensively, and biomarkers to predict the response to treatments were developed using clinical materials in various types of malignancies. For example, proteomics identified a strong biomarker candidate, pfetin, as a novel prognostic biomarker in gastrointestinal stromal tumor, where the anticancer drug became available to reduce the risk of post-operative metastasis. The prognostic utility of pfetin was immunohistochemically established by multi-institutional validation studies, and we expect that in the near future we will be able to select patients who may need adjuvant therapy by measuring the expression of pfetin in surgical specimens. These observations suggested the utility of proteomics for biomarker development. Other than the application of advanced technologies, the key points in biomarker studies are the use of an adequate number of clinical materials with problem-oriented experimental designs. Collaborations between basic researchers and clinicians are critical for the effective approach towards realistic biomarkers by proteomics.
癌症是一种在基因和临床方面具有多样性的疾病，治疗策略应针对个体病例进行优化。药物基因组学的最新进展催生了分子靶向抗癌药物，如何优化使用这些药物是一个新出现的挑战。生物标志物是评估肿瘤细胞恶性潜能和建立风险分层治疗的关键工具。蛋白质组是基因组的功能翻译产物，它直接调控肿瘤细胞的恶性表型；因此，蛋白质组学方法可为生物标志物的开发做出重大贡献。在过去十年中，蛋白质组学技术有了广泛进展，利用各种恶性肿瘤的临床材料开发出了预测治疗反应的生物标志物。例如，蛋白质组学确定了一个强有力的生物标志物候选物——pfetin，作为胃肠道间质瘤中的一种新型预后生物标志物，在这种肿瘤中已有抗癌药物可降低术后转移风险。通过多机构验证研究免疫组化证实了pfetin的预后效用，我们预计在不久的将来，我们将能够通过检测手术标本中pfetin的表达来选择可能需要辅助治疗的患者。这些观察结果表明蛋白质组学在生物标志物开发方面的效用。除了应用先进技术外，生物标志物研究的关键点在于使用足够数量的临床材料并采用以问题为导向的实验设计。基础研究人员和临床医生之间的合作对于通过蛋白质组学有效开发实用生物标志物至关重要。
