Dr. Ashwani K. Sood joined the staff of Roswell Park Comprehensive Cancer Center in 1983 as a cancer research scientist in the Department of Immunology. In 2001 he was named as assistant member of the department. He also participates as a faculty member with the University at Buffalo. Previous to joining Roswell Park he was a member of the Department of Human Genetics at Yale University.
Dr. Sood’s laboratory first reported that PDEF (prostate derived Ets factor, a member of the Ets family of transcription factors) is overexpressed in >80% of human breast tumors. Further, down regulation of PDEF reduces tumor cell survival in vitro and its transfection induces increased growth of breast epithelial cell lines in vitro and in immuno deficient mice. Moreover, elevated PDEF expression in primary tumors correlates with poor overall survival of breast cancer patients.
Together, these results showed that PDEF is a highly active novel oncogene in breast cancer. Additionally, PDEF expression is induced early in the precancerous ADH and DCIS lesions and maintained in invasive breast tumors and in lymph node metastases. These results provide a compelling rationale to evaluate PDEF as a target/antigen for primary prevention and treatment of breast cancer.
Towards this goal, we have found that immunization with Pse (prostate specific Ets, the mouse homolog of PDEF) induces specific T cell responses with anti-tumor activity in a mouse model of breast cancer. Moreover, we find that PDEF sequence contains three immunogenic peptides that induce specific T cell responses in HLA-A2/Kb transgenic mice in the context of HLA-A2. These results strongly support the development of PDEF based vaccines and T cell therapies for primary prevention and treatment of breast cancer.
Additionally, the mechanism(s) underlying the oncogenic action of PDEF in breast cancer remain poorly understood. Our studies on PDEF regulated genes identified CEACAM6 as a PDEF-induced molecule. Further characterization showed that similar to PDEF, CEACAM6 also has oncogenic role in breast cancer. These results provide further rationale for developing PDEF and CEACAM6 based vaccines and immunotherapies against breast cancer.
Sood, A.K., Geradts J and Young J. Prostate-derived Ets factor, an oncogenic driver in breast cancer. Tumor Biol 2017, 39: 1-6 PMID: 28468594
Mukhopadhyay A, Khoury T, Stein L, Shrikant P, Sood A.K. Prostate derived Ets transcription factor and Carcinoembryonic antigen related cell adhesion molecule 6 constitute a highly active oncogenic axis in breast cancer. Oncotarget. 2013; 4:610-21.
Ghadersohi A and Sood A.K. Prostate epithelium-derived Ets transcription factor mRNA is over expressed inhuman breast tumors and is a candidate breast tumor marker and a breast tumor antigen. Clin. Cancer Res. 2001; 7:2731-2738.
Hsu, S-C., Glaves-Rapp, D. and Sood, A.K. IL-2 secretion by KHT sarcoma cells leads to loss of their vaccine potential. Cancer Immunol. Immunother. 1997; 44: 117-124. PMID: 9177474.
Chakravarty, P., Fuji, H., Abu- hadid , M.M. Hsu, S-C. and Sood, A.K. Tumorigenicity of IL-2 cDNA-transfected L1210 lymphoma and its in vivo variants is modulated by changes in IL-2 expression; potential therapeutic implications. Cancer Immunol. Immunother. 1992; 35: 347-354 PMID: 1394339.