Kaposi's Sarcoma (KS) is now the leading cancer in males (48% of registered cases) and the second most common cancer in females (18%) in Kampala, Uganda and is equally prevalent in Kenya. This parallels the evolution of the AIDS epidemic. Based on epidemiological data there is high Kaposi's Sarcoma herpesvirus (KSHV)-seroprevalence in East Africa, and KSHV is the causative agent of the disease. KSHV is known to have several proto-oncogenes and infect dermal microvascular endothelial cells. There is up-regulation of PDGF-R and c-kit and increased proliferation in the presence of ligand such as platelet-derived growth factor (PDGF) and stem cell factor (SCF). It is therefore hypothesized that inhibition of PDGF-R and c-kit by the specific receptor tyrosine kinase antagonist imatinib will result in decreased proliferation and change in KS cells and lesions. A multidisciplinary and highly interactive team of investigators from Case Western Reserve University (Case) and two institutions in East Africa including the Uganda Cancer Institute (UCI) in Kampala and the Kenyatta National Hospital (KNH) in Nairobi, Kenya has embarked on a steadily productive international research collaboration dedicated to AIDS-related malignancy. This partnership now spans more than 6 years and bridges several NIH-funded centers of research excellence at Case led by the Center for AIDS Research (CFAR) and AIDS-Associated Malignancies Working Group, the NCI-designated Case Comprehensive Cancer Center and Developmental Therapeutics Program, and the Fogarty AIDS International Training and Research Program (AITRP). It is the intent of this application to continue to build on this effort to expand activities by virtue of exploring new, highly translational research trials that provide the springboard for pragmatic technology transfer, training of clinical and research personnel, and to explore the fundamental biology and pathogenesis of AIDS KS in a region of the world hardest hit by the epidemic. This application is directly responsive to two of the seven specific AIDS research priority areas (Area 1 International; and Area 5: Malignancies) outlined in the Program Announcement CFAR Competitive Supplements in AIDS-FY2005 Awards, which has been selected from among a competitive solicitation at our institution. Dr. Jackson Orem Senior Registrar at the Uganda Cancer Institute in Kampala, who has recently served a Fogarty Clinical Research- Scholarship at Case, leads this pilot study. It is envisioned, that successful completion of this pilot Phase II study, will readily lend itself to successor NIH-supported R21 / R01 / U01-type research grants in AIDS-related KS. ? ?
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