Vladimir Kolenko, MD, PhD
- PhD, Institute for Vaccines and Sera, Moscow, Russia, 1990
- MD, Academy of Medicine, Moscow, Russia, 1986
- Resistance to multitargeted receptor tyrosine kinase inhibitors (TKIs) in genitourinary tumors
- Therapeutic potential of piperlongumine and its derivatives
- Therapeutics of XIAP degradation by zinc chelators
- The role of zinc in prostate carcinogenesis
Our research efforts span the basic and the clinical sciences. In the laboratory, our work focuses on understanding the process of renal and prostatic carcinogenesis and assessing novel therapeutic regimens for the treatment of urological cancers. As part of our work, we study the mechanism of tyrosine kinase inhibitor (TKIs)-resistance in genitourinary tumors. Our studies reveal that TKI-resistance coincides with the loss of phosphatase and tensin homolog (PTEN) protein expression in prostate and renal malignant cells. Conversely, expression of PTEN sensitizes prostate and renal tumors to multi-targeted tyrosine kinase inhibitor sunitinib both in vitro and in vivo. In addition, our studies indicate that an increase in expression of IL-6 and IL-8 correlates with sunitinib and pazopanib resistance in prostate and renal tumor cells. Development of reliable biomarkers for TKI responses would be beneficial both in the clinical and in the research settings.
We are also investigating the role of zinc chelators as potential therapeutic agents for the treatment of castration-resistant prostate cancer. Findings from our laboratory indicate that treatment of prostate cancer cells with zinc-chelating agents induces selective down-regulation of X-linked inhibitor of apoptosis protein (XIAP) and sensitizes cancer cells to cytotoxic agents.
Our recent studies are also exploring the therapeutic potential of piperine and piperlongumine, alkaloids isolated from black and long pepper, for primary and secondary prevention of urologic malignancies.
Petr Makhov, MD, PhD
Research Assistant Professor
Golovine, K., Makhov, P., Uzzo, RG., Kutikov, A., Kaplan, DJ, Fox, E., Kolenko, V. Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-kappaB-independent, proteasome-mediated mechanism. Molecular Cancer. 9:183, 2010. PubMed
Makhov, P., Kutikov, A., Golovine, K., Uzzo, R.G., Canter, D.J., Kolenko, V. Docetaxel-mediated Apoptosis in Myeloid Progenitor TF-1 Cells is Mitigated by Zinc: Potential Implication for Prostate Cancer Therapy. The Prostate. 71(13):1413-9, 2011. PubMed