Translational Program - Urological Cancers
To understand molecular mechanisms of urological malignancies with the ultimate goal of improved treatment and diagnosis. Vision for our program is based on the holistic view that integration of basic research and clinical sciences is critically important for achieving the goal.
Current programmatic focus includes prostate, kidney cancer, and bladder cancer. The overall goal of the program is to understand molecular, biochemical, biological, and genetic mechanisms underlying tumor progression of these cancers and develop better diagnostic and treatment strategies. Molecular targets and pathways include Actin/Abi1/WAVE complex, HSP90, and TIMP. Clinically important questions are being addressed using multidisciplinary approaches and the state of-the-art equipment wherever possible. The program uses patient-derived tumor tissues and diverse in vivo models (GEMMs, xenografts, explants, organoid 3D-, and 2D- cultures).
Prostate cancer research focuses on number of critical problems such as understanding genetic and molecular mechanisms of prostate tumor progression from indolent to invasive tumors and androgen deprivation therapy resistance. The research projects evolve around defining the role of actin and actin polymerization regulatory complexes such as ABI1-WAVE, the role of cell-cell adhesion in tumor development, the role of Matrix Metalloproteases (MMPs) and their endogenous inhibitors (TIMPs) in tumor invasion. Other projects include the role of cell cycle in tumor progression and potential contribution of Plk1 and Aurora A kinase signaling to metastatic prostate cancer. Another project attempts to delineate the mechanism of chromosomal instability leading to gene fusions such as TMPRSS2-ERG fusions which are frequently found in prostate tumors.
Kidney cancer research focuses on developing novel therapies targeting the key molecular chaperone Heat Shock Protein-90 (HSP90), which critical to the folding, stability and activity of many proteins known as "client proteins" including many responsible for tumor initiation, progression and metastasis. Inhibition of Hsp90 leads to simultaneous inhibition of a broad range of oncogenic pathways. The research focuses on post-translational modifications of Hsp90 and the reciprocal regulatory mechanisms between the "kinase clients" and Hsp90.
Several clinical trials focused on improved treatment of urological malignancies are active at Upstate Cancer Center (here: website link for clinical trials). Notably, investigator initiated trial includes the protocol for collection of patient tissue: "Collection of Biospecimens from Patients with Biopsy-Proven or Suspected Urologic Malignancies" (Bratslavsky, PI, IRB No. 387215).
Integration of the TPUC with translational medicine involves collaborations with several clinical departments: Medicine, Hem/Onc (Drs. Graziano, Poeisz, Gajra, Benjamin), Radiation Oncology (Drs. Hahn, Bogart), and Pathology (Drs. Corona, DelaRoza, Landas) as well as Public Health and Preventive Medicine (Drs. Stewart and Formica).
Leszek Kotula, MD, PhD
Biochemistry & Molecular Biology