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.

在过去的一年里，我一直在招募研究人员在实验室工作， 和技术人员，并开始建立几个研究领域。主要研究领域 是非小细胞肺癌中EGFR抑制剂耐药的机制， 通过干扰阻止凋亡的分子（Bcl-2家族和抑制剂）来抑制凋亡 凋亡蛋白）。新的分子有可能逆转或规避 对EGFR抑制剂的耐药性正在测试中，作用机制正在阐明。基于 在先前的非小细胞肺癌切除样本的研究中，我们鉴定了HSP-90， 是一个重要的预后标志物，也是体外治疗的重要靶点， HSP-90抑制剂将在我以前开发的体外筛选系统中进行测试。 药物开发的其他领域，特别是与EGFR耐药相关的是c-Met和Trk， 新疗法的靶点。此外，我建立了大量的基因组研究 非小细胞肺癌、小细胞肺癌和胸腺瘤的患者样品， 为了更好地了解这些肿瘤中存在的遗传变异性， 临床信息，并最终确定潜在的目标， 治疗学在临床上，我已经建立了所有胸部恶性肿瘤的临床研究， 包括肺癌（非小细胞和小细胞肺癌）、间皮瘤、胸腺瘤。的 临床开发的重点是新药的早期开发，特别是 在EGFR抑制剂和调节剂难治性患者中有效的药物 细胞凋亡。立即开放的是Bcl-2小分子抑制剂的II期研究 在小细胞肺癌中。临床研究的另一个领域是疫苗接种的发展 非小细胞肺癌的治疗策略和免疫调节剂。我是两个大公司的私家侦探 研究寡核苷酸疫苗接种策略的随机III期研究 另一项研究调查了Talactoferrin，乳铁蛋白的类似物， 免疫调节剂。一个胸部肿瘤委员会最近开始活动， 主要器官专家下一阶段将包括启动多学科研究 在临界可手术非小细胞肺癌的新辅助治疗领域， 食道癌此外，我正在重组跨研究所肺癌小组， 促进合作和新项目的范围。其中一个已经在 肺癌干细胞的发展。

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

Strategies for overcoming resistance to EGFR family tyrosine kinase inhibitors.

• DOI: 10.1016/j.ctrv.2011.01.003
• 发表时间: 2011-10
• 期刊: CANCER TREATMENT REVIEWS
• 影响因子: 11.8
• 作者: Giaccone, Giuseppe;Wang, Yisong
• 通讯作者: Wang, Yisong