Stephen Hahn, M.D.
In collaboration with Eric Bernhard, Ph.D., Anjali Gupta, M.D., Ruth Muschel, and W. Gillies McKenna, M.D., Ph.D.: investigating targeting of the Ras-PI3K-Akt signaling pathway as a means to overcome radiation resistance. This group has shown that signaling through PI3K and Akt is an important determinant of radiation response. They have expanded their work and have shown that Ras-PI3K-Akt pathway activation is associated with tumor microenvironmental changes that alter radiation sensitivity. They have also shown in the past year that activation of this pathway is associated with poorer outcome in locally advanced NSCLC. Two prospective tissue acquisition trials in pancreatic cancer and NSCLC are ongoing to confirm these findings. Two Phase I clinical trials are underway in which this signaling pathway is targeted with the farnesyltransferase inhibitor, R115777 with radiotherapy in patients with NSCLC and pancreatic cancer.
In collaboration with Eli Glatstein M.D, Theresa Busch Ph.D., and Sydney Evans, VMD: evaluating the use of photodynamic therapy (PDT) for intraperitoneal and pleural cancers. They have recently reported that significant heterogeneity exists in photosensitizer uptake and tissue oxygenation in patients with peritoneal carcinomatosis. They have also demonstrated the ability to non-invasively measure using novel imaging techniques the optical properties, oxygenation, and photosensitizer uptake in patients with peritoneal carcinomatosis. A manuscript reporting the results of intraperitoneal PDT in 100 patients with peritoneal carcinomatosis is being prepared. Future plans are to evaluate new photosensitizers to determine the specificity of tumor uptake of these agents compared to normal tissues. This group has recently reported the encouraging results of PDT for patients with pleural spread of NSCLC. A competitive renewal of Dr. Glatstein's PO1 "Optimization of intraperitoneal PDT" will be submitted in the next year and will include intraperitoneal and pleural PDT.
In collaboration with Timothy Zhu, Ph.D.: evaluating PDT for patients with locally recurrent prostate cancer. They have demonstrated using novel imaging techniques that there is substantial heterogeneity in the optical properties, light distribution, oxygenation, and drug uptake in the human prostate. A new area of investigation is the use of optical tomography to develop a 3-dimensional image of the optical properties, oxygenation, and drug uptake in the human prostate. Dr. Timothy Zhu has been awarded a Department of Defense Grant and an RO1 from the National Cancer Institute to pursue this work and to develop a real-time dosimetry method to account for optical property heterogeneity.
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