Thoracic Cancer Research Laboratory

胸部癌症研究实验室

• 批准号: 8763425
• 负责人: Giuseppe Giaccone
• 金额: $ 108.45万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8763425
• 关键词: Adjuvant; Adjuvant Chemotherapy; Autoimmune Diseases; Biology; Chest; Clinical Research; Core Facility; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Fluorescent in Situ Hybridization; Freezing; Generations; Genes; Heat-Shock Proteins 90; Incidence Study; International; Laboratories; Lung Adenocarcinoma; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of thorax; MicroRNAs; Modification; Molecular Profiling; Mutation; Non-Small-Cell Lung Carcinoma; Oncogenes; Paraffin Embedding; Patients; Pattern; Prognostic Factor; Prognostic Marker; Publishing; RNA Sequences; Randomized; Resected; Resistance; Risk; Sampling; Second Primary Cancers; Sequence Analysis; Squamous cell carcinoma; Surrogate Markers; TP53 gene; Technology; Thymic Carcinoma; Thymoma; Thymus Neoplasms; Tumor Markers; anticancer research; deep sequencing; drug development; exome sequencing; follow-up; inhibitor/antagonist; meetings; mutant; novel; outcome forecast; population based; response marker; therapeutic target; translational study; tumor

Project 1: Translational studies in lung cancer. To investigate miRNA influence on prognosis and prediction of effect of adjuvant chemotherapy in radically resected non-small cell lung cancer (NSCLC) in the International Adjuvant Lung Cancer Trial (IALT), a randomized study of adjuvant chemotherapy vs. follow-up. To investigate associations of miRNAs and prognosis in lung adenocarcinoma vs. squamous cell carcinoma. To investigate if miR-21 expression is increased in EGFR mutant tumors. To investigate if miR-34a,b,c expression levels correlate with p53 status and p53 mutant tumors have reduced miR-34 expression. To investigate if let-7 has a stronger association with prognosis in wild-type K-Ras tumors. The study has been completed and published. None of the seven selected microRNAs had a significant correlation with survival or association with K-RAS or P53 mutations. Project 2: Translational studies in thymic malignancies. To study the incidence of thymomas compared to matched controls and also to assess survival patterns as well as risks of autoimmune diseases and secondary malignancies using a comprehensive population-based study. This study has been completed and published. The major findings was that younger patients have a poorer prognosis and that thymomas have a worse prognosis than matched controls. Project 3: Clinical studies in thoracic malignancies. To develop target agents that overcome resistance to EGFR TKIs, in particular, second-generation EGFR inhibitors, Met inhibitors, and HSP-90 inhibitors. Investigate novel agents in patients with advanced thymoma and thymic carcinoma. Study the tumor and surrogate markers of activity, to better identify patients who may benefit from treatment with targeted agents. Project 4: Therapeutic targets in thymic malignancies To perform CGH and RNA sequencing and exome sequencing on paraffin-embedded tumors and frozen tumors from patients with advanced thymic malignancies. To identify potential gene modifications (amplifications, translocations, mutations, etc.) that might be relevant as prognostic factors and or targets for systemic treatment.

项目1：肺癌的翻译研究。为探讨miRNA对根治性切除非小细胞肺癌(NSCLC)预后的影响及对辅助化疗疗效的预测，在国际辅助肺癌试验(IALT)中进行了一项辅助化疗与随访的随机研究。目的探讨肺腺癌和肺鳞癌中miRNAs与预后的关系。目的：探讨在EGFR突变肿瘤中miR-21的表达是否增加。目的：探讨miR-34a、b、c表达水平是否与P53状态及P53突变肿瘤是否降低miR-34表达有关。探讨let-7与野生型K-RAS肿瘤的预后是否有更强的相关性。这项研究已经完成并发表。所选择的7个microRNAs中没有一个与生存或与K-RAS或P53突变相关。项目2：胸腺恶性肿瘤的翻译研究。通过一项基于人群的综合研究，研究胸腺瘤的发病率与匹配对照组的比较，并评估生存模式以及自身免疫性疾病和继发性恶性肿瘤的风险。这项研究已经完成并发表。主要的发现是，与匹配的对照组相比，年轻患者的预后更差，胸腺瘤的预后更差。项目3：胸部恶性肿瘤的临床研究。开发靶向药物以克服对EGFR TKIs的耐药性，特别是第二代EGFR抑制剂、Met抑制剂和HSP-90抑制剂。研究治疗晚期胸腺瘤和胸腺癌患者的新药物。研究肿瘤和活性的替代标记物，以更好地识别可能从靶向药物治疗中受益的患者。项目4：胸腺恶性肿瘤的治疗靶点：对晚期胸腺恶性肿瘤患者的石蜡包埋肿瘤和冰冻肿瘤进行CGH和RNA测序以及外显子序列测定。识别潜在的基因修改(扩增、易位、突变等)这可能是相关的预后因素和/或系统治疗的目标。

项目成果

Personalizing therapy in an epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer using PF-00299804 and trastuzumab.

• DOI: 10.1200/jco.2010.29.3126
• 发表时间: 2010-10-01
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Kelly RJ;Carter C;Giaccone G
• 通讯作者: Giaccone G

Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients.

• DOI: 10.2217/pgs.10.172
• 发表时间: 2011-03
• 期刊: Pharmacogenomics
• 影响因子: 2.1
• 作者: Lemos C;Giovannetti E;Zucali PA;Assaraf YG;Scheffer GL;van der Straaten T;D'Incecco A;Falcone A;Guchelaar HJ;Danesi R;Santoro A;Giaccone G;Tibaldi C;Peters GJ
• 通讯作者: Peters GJ

Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer.

• DOI: 10.1371/journal.pone.0010630
• 发表时间: 2010-05-14
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hwang JH;Voortman J;Giovannetti E;Steinberg SM;Leon LG;Kim YT;Funel N;Park JK;Kim MA;Kang GH;Kim SW;Del Chiaro M;Peters GJ;Giaccone G
• 通讯作者: Giaccone G