Lung Cancer Program

肺癌计划

• 批准号: 7733285
• 负责人: Giuseppe Giaccone
• 金额: $ 129.56万
• 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/7733285
• 关键词: Apoptosis; Area; Chest; Clinic; Clinical; Clinical Research; Collaborations; Development; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Family; Fostering; Genetic; Genomics; Goals; Heat-Shock Proteins 90; Immunomodulators; In Vitro; Institutes; Laboratories; Lactoferrin; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Medical Oncology; Mesothelioma; Neoadjuvant Therapy; Non-Small-Cell Lung Carcinoma; Oligonucleotides; Organ; Patients; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Prognostic Marker; Randomized; Recruitment Activity; Refractory; Research; Research Personnel; Resected; Resistance; Sampling; Screening procedure; Specialist; System; Testing; Thoracic Neoplasms; Thymoma; Transforming Growth Factor beta; United States National Institutes of Health; Work; analog; base; cancer stem cell; cohort; drug development; inhibitor-of-apoptosis protein; inhibitor/antagonist; lung small cell carcinoma; multidisciplinary; novel; novel therapeutics; prevent; programs; resistance mechanism; small molecule; stem; tumor; vaccination strategy

In the last year I have been recruiting researchers to work in the laboratory, postdocs and technicians, and started builing up several areas of research. The main areas of research are mechanisms of resistance to EGFR inhibitors in non-small cell lung cancer, and modulation of apoptosis by interfering with molecules that prevent apoptosis (Bcl-2 family and inhibitor of apoptosis proteins). Novel molecules that have the potential of reversing or circumventing resistance to EGFR inhibitors are being tested and the mechanism of action elucidated. Based on previous work in resected non-small cell lung cancer samples, where we identified HSP-90 to be an important prognostic marker and also an important target for therapy in vitro, novel HSP-90 inhibitors will be tested in an in vitro screening system that I developed previously. Other areas of drug development, related partically to EGFR resistance are c-Met adn Trk as targets of novel therapeutics. Furthermore, I set up genomic studies on large cohorts of patient samples of non-small cell lung cancer, small cell lung cancer and thymoma, with the aim of better undestanding the genetic variability present in these tumors, correlate it with the clinical information available and eventually identify potential targets for novel therapeutics. In the clinic, I have set up clinical studies in all malignancies of the chest, including lung cancer (non-small cell and small cell lung cancer), mesothelioma, thymoma. The emphasis in clinical development is on early phase development of novel agents, in particular those that can be effective in patients who are refractory to EGFR inhibitors and modulators of apoptosis. Of immediate opening is a phase II studies of a Bcl-2 small molecule inhibitor in small cell lung cancer. Another area of clinical research is the development of vaccination strategies and immunomodulators in non-small cell lung cancer. I am the PI of two large randomized phase III studies that investigate a vaccination strategy with an oligonucleotide against TGFbeta and another study that investigates Talactoferrin, analogue of lactoferrin as immunomodulator. A thoracic tumor board has recently started activities, and includes the major organ specialists. The next phase will include activation of multidisciplinary studies in the area of neoadjuvant treatment of borderline operable non-small cell lung cancer and esophageal cancer. Furthermore, I am reorganizing the cross institute lung cancer group, with the scope of fostering collaborations and novel project. One of these has been on the development of lung cancer stem cells.

去年，我一直在招募研究人员在实验室工作、博士后和技术人员，并开始建立多个研究领域。主要研究领域是非小细胞肺癌对 EGFR 抑制剂的耐药机制，以及通过干扰阻止细胞凋亡的分子（Bcl-2 家族和细胞凋亡蛋白抑制剂）来调节细胞凋亡。正在测试具有逆转或规避 EGFR 抑制剂耐药性潜力的新型分子，并阐明其作用机制。根据之前对切除的非小细胞肺癌样本的研究，我们确定 HSP-90 是一种重要的预后标志物，也是体外治疗的重要靶点，新型 HSP-90 抑制剂将在体外筛选系统中进行测试我之前开发的。 与 EGFR 耐药相关的其他药物开发领域包括作为新疗法靶点的 c-Met 和 Trk。此外，我对大量非小细胞肺癌、小细胞肺癌和胸腺瘤患者样本进行了基因组研究，目的是更好地了解这些肿瘤中存在的遗传变异性，将其与现有的临床信息和相关性联系起来。最终确定新疗法的潜在靶点。在临床上，我对所有胸部恶性肿瘤进行了临床研究，包括肺癌（非小细胞和小细胞肺癌）、间皮瘤、胸腺瘤。临床开发的重点是新型药物的早期开发，特别是那些对 EGFR 抑制剂和细胞凋亡调节剂耐药的患者有效的药物。立即启动的是 Bcl-2 小分子抑制剂治疗小细胞肺癌的 II 期研究。临床研究的另一个领域是非小细胞肺癌疫苗接种策略和免疫调节剂的开发。我是两项大型随机 III 期研究的 PI，这两项研究研究了针对 TGFbeta 的寡核苷酸的疫苗接种策略，另一项研究则研究了 Talactoferrin（乳铁蛋白类似物）作为免疫调节剂的作用。胸部肿瘤委员会最近开始了活动，其中包括主要器官专家。下一阶段将包括在可手术的非小细胞肺癌和食管癌的新辅助治疗领域启动多学科研究。此外，我正在重组跨研究所肺癌小组，其范围是促进合作和新项目。其中之一是肺癌干细胞的开发。

项目成果

Role and relevance of TrkB mutations and expression in non-small cell lung cancer.

• DOI: 10.1158/1078-0432.ccr-10-3034
• 发表时间: 2011-05-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Harada T;Yatabe Y;Takeshita M;Koga T;Yano T;Wang Y;Giaccone G
• 通讯作者: Giaccone G

The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo.

• DOI: 10.1158/1078-0432.ccr-13-1110
• 发表时间: 2013-12-15
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Lee JH;Park KS;Alberobello AT;Kallakury B;Weng MT;Wang Y;Giaccone G
• 通讯作者: Giaccone G

A phase I/II trial of belinostat in combination with cisplatin, doxorubicin, and cyclophosphamide in thymic epithelial tumors: a clinical and translational study.

• DOI: 10.1158/1078-0432.ccr-14-0968
• 发表时间: 2014-11-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Thomas A;Rajan A;Szabo E;Tomita Y;Carter CA;Scepura B;Lopez-Chavez A;Lee MJ;Redon CE;Frosch A;Peer CJ;Chen Y;Piekarz R;Steinberg SM;Trepel JB;Figg WD;Schrump DS;Giaccone G
• 通讯作者: Giaccone G

Multiorgan autoimmune manifestations associated with thymoma.

与胸腺瘤相关的多器官自身免疫表现。

• DOI: 10.1097/jto.0000000000000324
• 发表时间: 2015
• 期刊: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
• 作者: Thomas,Anish;Rajan,Arun;Berman,Arlene;Giaccone,Giuseppe
• 通讯作者: Giaccone,Giuseppe

Lung cancer vaccines.

肺癌疫苗。

• DOI: 10.1097/ppo.0b013e318233e6b4
• 发表时间: 2011
• 期刊: Cancer journal (Sudbury, Mass.)
• 作者: Kelly,RonanJ;Giaccone,Giuseppe
• 通讯作者: Giaccone,Giuseppe