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Program Co-Leaders |
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Cutaneous malignancies are the most common malignancies in the United States and represent a major health problem both for morbidity and quality of life. In addition to the risk of cutaneous malignancies for sun-exposed and genetically predisposed individuals, skin cancer is a side effect of other medical procedures, including PUVA therapy for psoriasis and immunosuppression for organ transplants, and lifestyle factors such as tanning parlor use. The Cutaneous Oncology Program aims to improve our understanding of the causes of the three main classes of cutaneous malignancies -- melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) -- together with developing areas of immunologically related cancers in the skin and neurodegenerative disorders that show common genetic origins with some skin cancers.
The program's 24 faculty members encompass strong representation from laboratory, population, and clinical sciences. This diverse, multidisciplinary group includes clinical members (dermatologists, pathologists, surgeons, and medical and radiation oncologists) with wide-ranging expertise in the diagnosis and management of cutaneous malignancies.
Overall, the program aims to link the clinical activities in melanoma and non-melanoma skin cancers with laboratory-based and epidemiologic efforts aimed at prevention, improved diagnosis, and treatment of these diseases. Major themes of the program include: chemoprevention in basal cell cancer, the molecular basis of solar UV and oxidative damage and repair, neurocutaneous disorders, the role of calcium and CD44 signaling pathways, proteases in matrix remodeling, modifier genes and animal models, targeted therapy using hammerhead ribozymes, and cancer gene identification through copy number and gene expression array analysis. Program members have a major interest in high-risk patients, especially hereditary malignant melanoma, basal cell nevus syndrome, xeroderma pigmentosum, and organ transplant patients.
The program has access to two large databases of individuals with malignant melanoma and T-cell lymphoma. The UCSF Melanoma Center, directed by Dr. Kashani-Sabet, is home to a patient database established in 1971 and initially used to study the natural history of melanoma at a time when there were limited therapeutic options. It now has prospectively entered and followed over 10,000 patients and is a powerful tool for prognosis, as well as to examine important patient subsets based on histologic features. Using this database, program investigators have found novel, unexpected factors that appear to play an important role in the progression of human melanoma. With new technologies coming on line, the database will be indispensable to studies of molecular determinants of tumor progression in melanoma.
Through close interaction with the UCSF Department of Dermatology, an additional large archive of biopsy tissue is available for research. The database of archival specimens is linked to both primary and secondary diagnoses relevant to more than 45,000 accessions received every year. The volume of cases is particularly enriched by unusual neoplasms that are relevant to investigations of cutaneous cancers.
Program members use techniques such as comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), and gene expression arrays for molecular characterization of the malignant cancer phenotype, and development of novel mouse strains through targeted mutagenesis. Using the databases of melanoma and T-cell lymphoma, investigators are examining the impact of molecular determinants of tumor progression on metastasis and survival. The identification of genes involved in tumor progression has resulted in a major effort to develop molecular therapeutics for cutaneous malignancies. Current strategies use techniques such as short-interfering RNA (siRNA) and hammerhead ribozymes to inhibit expression of genes potentially associated with SCC and melanoma progression. Both targeted retroviral delivery systems and non-viral (cationic liposome) mediated approaches are being used.
Another important goal is to study the molecular mechanisms of cutaneous carcinogenesis, specifically in familial cancers (i.e., basal cell nevus syndrome), in photo-induced skin cancers (i.e., xeroderma pigmentosum), and in transgenic mice.
