Lung Cancer Program

在过去的一年里，我一直在招募研究人员到实验室工作，博士后和技术人员，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(Bcl2家族和凋亡抑制蛋白)来调控细胞凋亡。有可能逆转或规避对EGFR抑制剂耐药性的新分子正在进行测试，并阐明其作用机制。基于之前在切除的非小细胞肺癌样本中的工作，我们确定HSP-90是一个重要的预后标记物，也是体外治疗的重要靶点，新的HSP-90抑制剂将在我之前开发的体外筛选系统中进行测试。其他药物开发领域，特别是与EGFR耐药相关的c-Met和Trk是新疗法的靶点。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，目的是更好地了解这些肿瘤中存在的遗传变异，将其与现有的临床信息相关联，并最终确定新疗法的潜在靶点。在临床上，我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。临床开发的重点是新药的早期开发，特别是那些对EGFR抑制剂和凋亡调节剂无效的患者有效的新药。立即开始的是一项针对小细胞肺癌的Bcl-2小分子抑制物的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。我是两项大型随机第三阶段研究的PI，这两项研究调查了使用针对TGFbeta的寡核苷酸的疫苗接种策略，另一项研究调查了Talactoferrin，即乳铁蛋白的类似物，作为免疫调节剂。一个胸部肿瘤委员会最近开始了活动，成员包括主要器官专家。下一阶段将包括启动交界性可手术非小细胞肺癌和食道癌新辅助治疗领域的多学科研究。此外，我正在重组跨研究所肺癌小组，以促进合作和新项目的范围。其中之一就是肺癌干细胞的发展。

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.