PROTEOMIC ANALYSIS TO PREDICT CHEMOSENSITIVITY IN ANSCLC

通过蛋白质组学分析预测非小细胞肺癌的化疗敏感性

• 批准号: 7719073
• 负责人: SHAKUN M MALIK
• 金额: $ 0.14万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719073
• 关键词: Affect; Biological; Cancer Etiology; Cell Proliferation; Cessation of life; Class; Classification; Classification Scheme; Clinical; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Diagnosis; Disease; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Epigenetic Process; Epithelial; Erlotinib; Funding; Gefitinib; Gene Expression; Genetic; Genomics; Grant; Hematopoietic Neoplasms; Institution; Lead; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Molecular; Molecular Biology; Molecular Profiling; Mutation; Natural History; Outcome; Pathogenesis; Patients; Peptides; Pharmaceutical Preparations; Pilot Projects; Proteomics; Rate; Research; Research Personnel; Resources; Somatic Mutation; Source; Stem cells; Therapeutic; Time; Toxic effect; Translating; Treatment outcome; United States; United States National Institutes of Health; cancer classification; gene therapy; improved; lung Carcinoma; neoplastic cell; novel; prospective; response; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lung cancer is the leading cause of cancer death in the United States and worldwide. Yet despite the clinical importance of lung cancer, the detailed classification of lung carcinomas has lagged far behind those of the hematopoietic malignancies. Lung cancer is a highly heterogeneous clinical entity, with varying natural history and response to treatment. Despite efforts to identify histological sub-groups of patients, our ability to accurately predict therapeutic response remains poor. Our efforts are mitigated by the genetic complexity of lung tumors. Multiple somatic mutations and epigenetic changes influence the expression of genes affecting lung tumor cell proliferation, invasion, and metastatic potential. Expression profiles in a given tumor can be regarded as the outcome of complex influences resulting from the accumulated genetic changes important for the pathogenesis as well as from differentiation commitment of the progenitor cells. A better understanding of the molecular mechanisms underlying lung cancer etiology, pathogenesis, and therapeutics will lead to improved clinical outcomes. During the last several years, the advent of systematic genomic and proteomic approaches to cancer classification have begun to accelerate the discovery of new classification schemes for epithelial malignancies. The intensity of the study of lung carcinoma has been particularly strong. The advent of effective targeted therapies for lung cancer, such as the epidermal growth factor receptor inhibitors erlotinib and gefitinib, and the prospect of developing additional targeted therapies, has emphasized the importance of accurate diagnosis. This may facilitate the improvement of current therapeutics and the identification of novel targets. Taken together, these advances hold the promise of an improved understanding of the molecular biology of lung cancer and its treatment, which in turn will lead to improved outcomes for this deadly disease. A change of therapy including emerging new biological and gene therapies which have less systemic toxicities may be more appropriate in some of these patients. This is a prospective pilot study to identify peptide markers that predict chemosensitivity in patients that would correlate with treatment outcome. This will lead to change in therapy and will translate in the improvement in response rate, time to progression, and overall survival. We may also be able to identify new targets that can be used in the development of new classes of drugs in the treatment of lung cancer.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 肺癌是美国和全球癌症死亡的主要原因。尽管肺癌的临床重要性，但肺癌的详细分类却远远落后于造血恶性肿瘤。肺癌是一种高度异质的临床实体，具有不同的自然病史和对治疗的反应。尽管努力确定患者的组织学子组，但我们准确预测治疗反应的能力仍然很差。肺肿瘤的遗传复杂性减轻了我们的努力。多个体细胞突变和表观遗传变化影响影响肺部肿瘤细胞增殖，侵袭和转移潜力的基因的表达。给定肿瘤中的表达谱可以被视为由累积的遗传变化对发病机理以及祖细胞的分化承诺重要的复杂影响的结果。 更好地了解肺癌病因，发病机理和治疗剂的分子机制将改善临床结果。在过去的几年中，系统的基因组和蛋白质组学分类方法的出现已经开始加速发现上皮恶性肿瘤的新分类方案。肺癌研究的强度特别强。有效的针对肺癌靶向疗法的出现，例如表皮生长因子受体抑制剂Erlotinib和Gefitinib，以及开发其他靶向疗法的前景，强调了准确诊断的重要性。这可能有助于改善当前治疗剂和新靶标的识别。综上所述，这些进步使人们对肺癌及其治疗的分子生物学有了改善的理解，这反过来又将改善这种致命疾病的结果。在其中一些患者中，包括新的生物学和基因疗法（包括新的生物学和基因疗法）的变化可能更合适。这是一项前瞻性试点研究，旨在鉴定预测与治疗结果相关的患者化学敏感性的肽标志物。这将导致治疗的变化，并将转化在反应率，进展时间和整体生存期的改善中。我们也许还可以确定可以在肺癌治疗中用于开发新类药物的新靶标。