| Program Leader: C. Lee, PhD |
|
Program Co-Leader: W. Catalona, MD |
|
|
The Solid Tumor Investigations Program is a fully developed, highly interactive and productive program. The program consists of accomplished faculty conducting highly translational studies centered on the themes of molecular and cell biology, epidemiology, prevention, early diagnosis, prognosis, risk factors, therapeutics, quality of life, and outcomes research. The Program Leader is Chung Lee, PhD and the Co-Leader is William Catalona, MD, both eminent investigators with distinguished careers in Solid Tumor Investigations research, whose skills and expertise complement each other. The overall goal of the Solid Tumor Investigations Program is to coordinate and enhance the interactions among researchers in the area of Solid Tumor Investigations at Northwestern University. The importance of the Solid Tumor Investigations Program stems from the fact that Solid Tumor Investigations is the most frequently diagnosed cancer and the third leading cause of cancer death in men in the United States. During this past funding period the Solid Tumor Investigations Program has been enhanced by receiving a prestigious NCI award for a SPORE in Solid Tumor Investigations (P50 CA90386). SPORE funding has enabled Solid Tumor Investigations Program investigators to establish a tissue bank with specimens from over 1,500 consented patients, which is supported by a comprehensive clinical database. This important infrastructure has facilitated the initiation of at least ten translational research projects within as well as outside the Northwestern University community. This interdisciplinary Prostate Program consists of 25 faculty representing 12 departments and 3 schools. Between 1/1/2001 and 9/15/2006, there were 427 cancer-relevant publications from the current Protstate Cancer Program members. Seventy-One (17%) of these publications represent intra-programmatic collaborations and 94 (22%) of these publications represent inter-programmatic collaborations. Total current cancer relevant peer reviewed funding for the Solid Tumor Investigations Program is $5,168,930 (direct) with $2,527,780 (direct) from NCI, and $2,641,150 (direct) from other peer reviewed sources. The Robert H. Lurie Comprehensive Cancer Center provides the necessary infrastructure to further develop investigators productivity in Solid Tumor Investigations research. The interactions between investigators, which are facilitated by the Solid Tumor Investigations Program, are synergistic and essential for multidisciplinary intra- and inter-programmatic translational Solid Tumor Investigations research.
Back to top
Understanding the basic biology of the normal and cancerous prostate is critical for developing new approaches for diagnosis, prognosis, and treatment of prostate cancer. Several aspects of the basic prostate biology are studied by members of the Solid Tumor Investigations Program. One of the important aspects is the mechanism of prostate development (Lamm, Lee). The role of a set of conserved developmental genes including Sonic Hedgehog, hox genes, and BMP-4 genes are being studied. The prostate growth and morphogenesis is androgen-dependent. Stromal-epithelial and epithelia-extracellular matrix interactions are essential factors regulating prostate growth, differentiation and metastasis (Bergan, Lee) and angiogenesis (Crawford, Lee, Volpert). Epithelial to mesenchymal transition (EMT) is a key mechanism for cancer progression and metastasis. Investigation of the mechanisms of EMT has been studied by Drs. Goldman and Lee. Apoptosis in normal and cancerous prostate cells is also a major research interest of the members of the Solid Tumor Investigations Program (Chandel, Lee, Volpert). Considering the fact that skeletal Solid Tumor Investigations metastasis is very frequent, interactions between Solid Tumor Investigations cells and bone matrix are also studied by members of the Cancer Center (Kaul, Satcher, Stern, Woloschak). Promoter methylation in tumor suppressor genes has been associated with Solid Tumor Investigations progression (Kaul, Lee). Finally, members of the Solid Tumor Investigations Program are taking advantage of the emerging nanotechnology to elucidate prostate carcinogenesis, cancer progression, and androgen action (Meade, Mirkin, Woloschak). The goal of the above studies is to facilitate the development of new approaches for Solid Tumor Investigations management though elucidating the fundamental molecular mechanisms of proliferation, apoptosis, differentiation, and cell-cell interactions in both normal and cancerous prostate.
Back to top
Clinical facilities at Northwestern Memorial Hospital, the Jesse Brown VA Medical Center, and Evanston Northwestern Healthcare provide a basis for clinical diagnosis and early detection research (Kaul, Pins, Shevrin, Yang) that has a profound effect on Solid Tumor Investigations patients. Efficient identification of both hereditary and sporadic genetic mutations in Solid Tumor Investigations patients could assist physicians to detect aggressive prostate cancers at early stages (Catalona). The development of novel approaches for detecting DNA mutations is exciting in that new technologies are applied to Solid Tumor Investigations diagnosis (Barron). Finding circulating Solid Tumor Investigations cells in blood using a PCR method represents the state-of-the-art technology in Solid Tumor Investigations staging (Kaul, MacVicar). One of the challenging problems in Solid Tumor Investigations treatment is how to predict whether the patients will remain disease-free after radical prostatectomy. New markers including alpha methylacyl-CoA racemase (AMACR), adrenomedullin, clusterin, TGF-beta, and calreticulin (Bergan, Lee, Pins, Yang) are being studied for their predictive value for Solid Tumor Investigations recurrence after surgery. Research in the use of sensitive PSA assay (nano-PSA project) is a collaboration between Drs. Mirkin and Schaeffer. They will be able to determine the presence of minimal residual disease in patients following prostatectomy. Considering that the incidence of Solid Tumor Investigations is associated with life style, our investigators are also investigating the impact of dietary supplements on Solid Tumor Investigations risk factors (Bergan).
Back to top
There is a desperate need for novel therapies to treat metastatic prostate cancer. Although androgen ablation therapy is initially effective for patients with metastatic prostate cancer, patients eventually relapse with androgen-refractory prostate cancer. To prolong the life of patients with advanced prostate cancer, the members of the Solid Tumor Investigations Program are developing novel therapeutic approaches. One promising therapy is based on angiogenesis inhibitors (MacVicar, Volpert). Angiogenesis inhibitors block the blood supply of prostate tumors, leading to the regression or growth arrest of prostate tumors. Another approach being explored is direct modulation of prostate cell adhesion to prevent metastasis formation (Bergan). This is derived from a novel finding in the laboratory that genistein enhances cell adhesion of Solid Tumor Investigations cells. Clinical and laboratory investigations are ongoing. Gene therapies based on TGF-beta signaling pathways are also being explored (Kuzel, Lee). The possible complementation of these novel therapeutic approaches with the conventional therapeutic modalities will be pursued (Bergan, Kuzel, Schaeffer, Shevrin). One of the critical issues in Solid Tumor Investigations patient care is the quality of life including urinary function, sexual function, bowel function, pain, and nutrition. Members of the Solid Tumor Investigations Program are conducting population-based outcome research in Solid Tumor Investigations (Bennett, Shevrin). One of the major quality of life issue is post-radical prostatectomy erectile dysfunction (pRP-ED). Molecular mechanism of pRP-ED are being investigated (McVary), which may lead to novel approaches for intervention and prevention of pRP-ED.
Back to top
|
|
