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.
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