Prostate Cancer Center Research Lab

The completion of the human genome project in April 2003 engendered a new era of cancer research. The molecular analysis of cancer is now leading to new therapies termed molecular targeted therapies. With a focus on translational research, the mission of the research laboratory at the Louis Warschaw Prostate Cancer Center (LWPCC) is to facilitate the development of such molecular therapies for prostate cancer treatment and to incorporate their use within the current treatment options. To accomplish this mission of taking drug discoveries from bench top to bedside, the research laboratory assimilates both the basic traditional research tools of cellular/molecular biology as well as the more recent genomic and proteomic technologies.

The key scientific areas of LWPCC research focuses on development of prostate cancer treatment through understanding the biology of prostate cancer. The approach is two-fold: a) to develop preclinical models of prostate cancer that can be utilized to mimic clinical scenarios to study prostate tumor biology and treatment potentials of novel therapies at molecular levels, and b) to observe and adapt novel and unexpected outcomes from current clinical studies to preclinical models to improve upon the currently available therapies.

The research laboratory at the LWPCC is well-equipped and scientifically connected to perform a variety of cellular and molecular biology techniques to study clinical as well as preclinical tissues at both genomic and proteomic levels. These include high throughput molecular screening, fluorescent microscopy and imaging, lentivirus mediated gene expression and RNA interference assays, mass spectrometric based phosphoproteome analysis, primary tumor cell cultures, etc. The laboratory has a range of prostate cancer xenograft mouse models that capture various stages of prostate cancer. These xenograft model systems are utilized to evaluate the in vivo efficacy of novel therapeutics before these therapeutics move to clinical trials. The prostate cancer laboratory is frequently approached by several pharmaceutical and biotechnology companies to test their novel drugs in prostate cancer systems to identify the models demonstrating the best efficacy. This forms a starting point to develop tools for biomarker discovery as well as utility of such drugs in prostate cancer. In addition, the lab has derived therapeutic-related novel sublines from these xenograft systems that form important resources to study mechanisms of action of targeted therapeutics in prostate cancer treatment. Tissues from such studies are analyzed for biomarkers of therapeutic response or resistance. The laboratory has an in-house high-throughput real-time PCR system and an automated capillary DNA sequencer for quantitation and detection of nucleic acid sequences and single nucleotide polymorphisms respectively.

The research laboratory at the LWPCC is well-equipped and scientifically connected to perform a variety of cellular and molecular biology techniques to study clinical as well as preclinical tissues at both genomic and proteomic levels. These include highthroughput molecular screening, fluorescent microscopy and imaging, lentivirus mediated gene expression and RNA interference assays, mass spectrometric based phosphoproteome analysis, primary tumor cell cultures, etc. The laboratory has a range of prostate cancer xenograft mouse models that capture various stages of prostate cancer. These xenograft model systems are utilized to evaluate the in vivo efficacy of novel therapeutics before these therapeutics move to clinical trials. The prostate cancer laboratory is frequently approached by several pharmaceutical and biotechnology companies to test their novel drugs in prostate cancer systems to identify the models demonstrating the best efficacy. This forms a starting point to develop tools for biomarker discovery as well as utility of such drugs in prostate cancer. In addition, the lab has derived therapeutic-related novel sublines from these xenograft systems that form important resources to study mechanisms of action of targeted therapeutics in prostate cancer treatment. Tissues from such studies are analyzed for biomarkers of therapeutic response or resistance. The laboratory has an in-house high-throughput real-time PCR system and an automated capillary DNA sequencer for quantitation and detection of nucleic acid sequences and single nucleotide polymorphisms respectively.

Some of the current research projects in the laboratory are:

  • Role of epithelial-mesenchymal interactions in EGFR-pathway modulation and the activity of drugs targeting this pathway.
  • Evaluation of phosphorylation modifications on the EGFR signaling pathway with response or resistance to targeted therapeutics.
  • Chemotherapeutic resistance mechanisms in prostate cancer.
  • Functional interactions between EGFR and Androgen Receptor signaling pathways.
  • In vivo evaluations of PI3K and Raf inhibitors in androgen-independent prostate cancer.

Investigators at the LWPCC are part of the U54 Center of Cancer Nanotechnology Excellence Program funded by the NCI.

Selected recent publications from the LWPCC are:

  • *Laux, I., *Jain, A., Singh, S., and Agus, D. B. (2006). British J Cancer, 94, 85-92.
  • Shazer, R. L., Jain, A., Galkin, A. V., Cinman, N., Nguyen, K. N., Natale, R. B., Gross, M., Green, L., Bender, L. I., Holden, S., Kaplan, L., and Agus, D. B. (2006). BJU International. 97, 691-697.
  • *Jain, A., *Tindell, C., *Laux, I., Hunter, J., Curran, J., Galkin, A., Afar, D. E., Aronson, N., Shak, S., Natale, R. B., and Agus, D. B. (2005). PNAS, 102, 11858-11863.
  • Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G. (2005). J. Clin. Oncol., 23, 2534-2543
  • *Hedvat, M., *Jain, A., Mullen, L., Huang, G., Fox, W., Carson, D. A., Leoni, L. M., Agus, D. B. (2004). Cancer Cell, 5, 565-574

* co-first author