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Bulent Ozpolat

Bulent Ozpolat

The University of Texas-MD Anderson Cancer Center, USA

Title: siRNA-based targeted gene therapies in cancer: Targeting EF2-kinase in solid tumors

Biography

Bulent Ozpolat earned his M.D. in 1989 from Dokuz Eylül University in Izmir, Turkey. He moved to Houston in 1994 and enrolled in The University of Texas Graduate School of Biomedical Sciences at Houston where he obtained a Ph.D. in Immunology (1999), concentrating his efforts on the development of gene vaccines against breast cancer, immunoliposomal delivery systems for nucleic acids, cytokines, peptides and vaccine adjuvants. In 2000, he joined the laboratory of Immunobiology and Drug Carriers as a postdoctoral fellow under the mentorship of Dr. Gabriel Lopez-Berestein at MD Anderson where he furthered his career in cancer biology, particularly in the areas of leukemia and breast cancer, targeted therapies and nanovector delivery systems. He was promoted to the faculty position of Instructor in 2003 and Assistant Professor in 2008 in the Department of Experimental Therapeutics. In the past five years, Dr. Ozpolat has contributed to more than 20 manuscripts in peer-reviewed journals focusing on autophagic cell death (Type II programmed cell death), differentiation therapy, signal transduction and the development of targeted therapies. He has made significant contributions to the field through describing a new posttranscriptional mechanism of cell differentiation induced by retinoids; the mechanisms of autophagic cell death in breast and pancreatic cancers cells; and novel tumor-targeted carrier systems for siRNA, peptides for cancer therapy.

Abstract

After recent discovery, the use of small interfering RNA (siRNA) has rapidly become a powerful tool for silencing oncogenes and holds promise as a novel class of therapeutics in cancer. siRNA based therapeutic intervention can be uses especially for those targets that cannot be targeted by small inhibitors or for “non drugable” targets. However, successful clinical applications and in vivo delivery of the siRNA-based therapeutics to primary and metastatic tumors remains as a great challenge. We recently identified eEF2-kinase in solid tumorssuch as breast and pancreatic cancer developed tumor targeting nanoliposomes that can target siRNA in vivo into tumor cells more effectively than regular liposomes, leading to significant and robust target gene silencing for about a week in breast, ovarian and prostate cancers animal models. Overall, our preclinical studies demonstrated that highly specific targeting of genes promoting cell proliferation, survival, tumor growth, invasion ad progression including EF2-kinase (Ef2K) and Bcl-2, EphA2 genes by liposomal siRNA nanotherapeutics significantly inhibited tumor growth in breast, ovarian and prostate cancers, respectively, as well as hematological tumor models such as lymphoma. Our data suggest that siRNA based nanotherapies have potential as novel class of systemic therapies for various cancers and provide the proof of concept and the impetus for translational studies for Phase I clinical trials in patients.