The Hasan Program Project
Molecular Response and Imaging-based Combination Strategies for Optimal PDT
Edward V. Maytin, M.D., Ph.D.
Staff in Dermatology, Cleveland Clinic Foundation
Assistant Staff in Biomedical Engineering, Cleveland Clinic Foundation
Phone: 216-445-6676
Fax: 216-444-9198
E-mail: maytine@ccf.org
Role and Rationale in PPG
Non-melanoma skin cancers (NMSC), comprising squamous cell (SCC) and basal cell carcinomas (BCC), have a significant impact upon the health care system because their overall incidence is higher than for all other cancers combined. Therefore, while not usually fatal, these skin carcinomas incur a very high cost for their management, e.g., 90% of the cost of treating breast cancer. The current standard of care is surgical excision with wide margins. Major morbidity stems from fibrosis, scarring, and loss of function after treatment. Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) represents a non-disfiguring alternative to surgery, especially for patients with multiple tumors and for tumors in delicate sites. Currently, the efficacy of ALA-PDT is not adequate to realistically compete with surgery in the U.S.A.
Based on one of the Program themes of Combination Photodynamic Biologic Therapy (CPBT), in Project 1, our overall hypothesis is that tumor-differentiating agents can be used to improve the efficacy of ALA-PDT so that PDT becomes a viable alternative to surgery for NMSC. We will build upon our discovery that two small molecules, methotrexate (MTX) and vitamin D (Vit D), can increase tumor cell differentiation and at the same time increase the levels of photosensitizer (PpIX) within the cells, thus enhancing responsiveness to therapy. The project is translational in nature, with clinical and basic science components.
Aim 1 is preclinical, and uses mouse models of SCC and BCC to determine optimal dosing regimens for the systemic differentiating agent.
Aims 2 and 3 are clinical studies to determine the efficacy of topical Vit D and oral MTX as combination agents with ALA-PDT. These Aims will also test new in vivo multimodal subsurface imaging devices for PpIX detection, and evaluate C/EBP transcription factors ex vivo as prognostic markers of tumor response.
Aim 4 consists of mechanistic experiments that will examine regulatory functions and the prognostic value of the C/EBPs in terms of PpIX accumulation, using the preclinical models and examining tissue-banked skin tumor specimens from the clinical studies.
Positions held
- 1984. Ph.D., University of Rochester (Biophysics), Rochester, NY
- 1985. M.D., University of Rochester School of Medicine and Dentistry, Rochester, NY
- 1985-1986. Intern in Medicine, Roger Williams Hospital, Brown University, Providence, RI
- 1986-1987. Clinical and Research Fellow (Dermatology), Harvard Medical School, Boston
- 1987-1990. Resident in Dermatology, Harvard Medical School, Boston
- 1990-1995. Instructor of Dermatology, Harvard Medical School, Boston
- 1990-1999. Assistant in Dermatology, Massachusetts General Hospital, Boston
- 1993-1999. Research Fellow in Medicine (Endocrinology), Howard Hughes Medical Institute, Massachusetts General Hospital, Boston
- 1996-1999. Assistant Professor of Dermatology, Harvard Medical School, Boston
- 2000-. Assistant Staff in Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH
- 2000-. Staff in Dermatology, Cleveland Clinic Foundation, Cleveland, OH
- 2004-. Assistant Professor, Dept of Chemical & Biomedical Engineering, Cleveland State University, Cleveland, OH
- 2005-. Assistant Professor, Dept of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (CCLCM), Cleveland, OH
NIH Biosketch is available for download.
Major research interests
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