Function Based Therapeutic Strategies to Prostate cancer, Ewing Sarcoma, Breast cancer and leukemias.



Dr Shyam Reddy discovered and cloned several cancer genes/oncogenes (close to 20 genes) and studied their functions. The most notable genes discovered by Dr Reddy include ERG-1, ERG-2, ERG-3 and human FLI-1genes. Dr Reddy named the gene as ERG ( ETS Related Gene, published in prestigious journals Science and PNAS) . ERG is a transcriptional factor and also a stem cell factor and is involved in 50-80% of Prostate cancers, Ewing sarcoma and also leukemias (AML). Other notable ETS genes discovered and studied by Dr Reddy include human Fli-1 (involved in 80% of Ewing family of tumors, Leukemias and Prostate cancer), EWS-Fli-1 (involved in 80% of Ewing Sarcoma, Pediatric cancer), EWS-erg (involved in Ewing Sarcoma), TLS-erg (involved in Acute Myeloid Leukemia), EWS (involved in multiple cancers), TLS/FUS (involved in multiple cancers), ELK-1 (Drs Reddy and Rao named this gene as ETS Like Gene, published in prestigious journals Science and Nature), BRCA1a, BRCA1b, BRCA2a (involved in breast, ovarian and prostate cancers) and EWS-ATF-1 (malignant Melanoma of Soft Parts/Clear cell sarcoma)



 Dr Reddy and his group have shown that ERG and FLI-1 proteins involved in several cancers are responsible for making cancer cells resistant to chemo-therapeutic agents. They are targeting these onco-proteins or their functions to develop novel targeted therapeutic agents. Using this strategy, they have developed several novel drugs (patent being submitted) that target Prostate cancer, Ewing Sarcoma, Breast cancer (Triple Negative Breast Cancer), Pancreatic cancer, Ovarian cancer, cervical cancer, colorectal cancer, pancreatic cancer etc. These drugs appear to be targeted therapeutic agents with no or little effect on normal cells. Dr Reddy received a grant from DOD to do research on two drugs against prostate cancer. We are grateful to DOD organization for standing up to our cancer research. We have also shown that anti-epileptic drug Valproic acid (VPA) targets ERG-positive Prostate cancers and Children bone cancer and identified the molecular mechanism of action of VPA on ERG function. Recently, we have identified novel ways by which ERG/ETS oncoproteins target diffent signaling pathways that leads to prostate and other cancers (leukemias, lymphomas and sarcomas). Recently, we have identified novel molecular mechanism of activation of TGF beta–signaling pathway by ERG oncoprotein in prostate cancer. We are also studying the mechanism of action of successful novel drugs (that are presently being used in clinical trials) on prostate, breast and childhood cancers including their metastases.