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，博士后和技术人员中工作，并开始建立几个研究领域。研究的主要领域是非小细胞肺癌中对EGFR抑制剂抗性的机制，以及通过干扰预防凋亡的分子（BCL-2家族和凋亡蛋白抑制剂）来调节凋亡的调节。具有逆转或规避对EGFR抑制剂的耐药性的潜力的新型分子正在测试中，并阐明了作用机理。基于先前在切除的非小细胞肺癌样品中的工作，我们将HSP-90确定为重要的预后标记，并且在体外治疗的重要靶标，新型的HSP-90抑制剂将在我先前开发的体外筛查系统中进行测试。 药物开发的其他领域，部分与EGFR耐药性相关的是C-MET ADN TRK作为新型治疗剂的靶标。此外，我对非小细胞肺癌，小细胞肺癌和胸腺瘤的大量患者样本进行了基因组研究，以更好地消除这些肿瘤中存在的遗传变异性的目的，并将其与可用的临床信息相关，并最终识别出新型治疗方法的潜在靶标。在诊所中，我在胸部的所有恶性肿瘤中都建立了临床研究，包括肺癌（非小细胞和小细胞肺癌），间皮瘤，胸皮瘤。临床发育的重点是新型药物的早期发育，特别是那些对EGFR抑制剂和凋亡调节剂难治的患者有效的那些。立即开放的是小细胞肺癌中Bcl-2小分子抑制剂的II期研究。临床研究的另一个领域是非小细胞肺癌中疫苗接种策略和免疫调节剂的发展。我是两项大型随机III期研究的PI，这些研究研究了针对TGFBETA的寡核苷酸的疫苗接种策略，并研究了另一项研究，该研究研究了乳酸铁蛋白（乳酸铁蛋白的类似物）作为免疫调节剂的类似物。胸部肿瘤委员会最近开始了活动，其中包括主要风琴专家。下一阶段将包括在新辅助治疗可操作的非小细胞肺癌和食管癌的新辅助治疗领域的多学科研究。此外，我正在重组跨学院肺癌小组，并促进了合作和新型项目的范围。其中之一是肺癌干细胞的发展。

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

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