MCW Office of Technology Development

Prostate-specific antigen (PSA) is a serine protease used as a tumor marker to diagnose and evaluate the effectiveness of therapy for prostate cancer. PSA blood test results between 0 and 4 are within the normal range while a PSA over 10 indicates a potential problem which could include cancer, benign enlargement or inflammation of the prostate.
 
Current methods of treatment for prostate cancer depend on the tumor's stage and the age of the patient.  Surgery, radiation, and hormone therapy are the most common treatments for prostate cancer.  Hormone therapy may be used as an adjunct to surgery or when surgery is not a good option due to physical limitations, distant metastases, or recurrent disease. Hormone therapy lowers the levels of androgens including testosterone that cause prostate cancer cells to grow. Lowering androgen levels can make prostate cancer shrink or grow more slowly. Two examples of antiandrogens are flutimide and bicalutamide

Although the PSA test is widely used and is recommended by the American Cancer Society, it is important to note the test has low clinical specificity, producing substantial false positive readings. Frequently such men do not have prostate cancer, but instead have BPH, a treatable condition. Hence, there is a need for an "improved" tumor marker test that is more specific.

With hormonal therapy treatment of prostate cancer, while initially effective in the majority of patients, the disease ultimately becomes resistant to the loss of androgens (androgen-independent), returns and, in many cases, culminates in the death of the patient.

Obesity (adiposity) is associated with prostate cancer, particularly with its accelerated progression. Adipose factors including adiponectin, leptin, IGF and IL-6, are molecular mediators between prostate cancer and obesity. Researchers at the Medical College of Wisconsin have shown that leptin and other adipose factors such as IGF-1, IGF-II, TNF-alpha, and IL-6 stimulate prostate cancer cell growth and subsequent blockage of these adipose factors will suppress androgen-independent prostate cancer cell growth and increase survival. These adipose factor functions can be blocked by inhibiting their expression, the expression of their cell surface receptors, or by inhibiting the binding of these cytokines to their receptors. In addition, the adipose factor adiponectin demonstrates an inhibitory effect of on cell growth and cell viability in prostate cancer and hepatocellular carcinoma cells. Adiponectin inhibits stimulatory adipose cytokine (leptin and/or IGF-I)-induced prostate cancer cell growth indicating that adiponectin competes with stimulatory adipose factors to inhibit prostate cancer cell growth. Dr Iwamoto also demonstrates that adiponectin enhances doxorubicin-induced cell growth inhibition in prostate cells suggesting that f-adiponectin can be used for adjuvant therapy in combination with such existing therapeutic interventions as anti-cancer drugs and irradiation. Adiponectin modulates a novel signaling pathway that effects the activation of JNK and STAT3, signaling molecules implicated in both cancer and metabolic disorders.  Dr. Iwamoto also identifies leptin-regulated genes, including adiponectin receptor 1 gene, that are crucial in androgen-independent prostate cancer cell growth. 

•    Adipose factors provide novel targets and therapeutics for treating obesity relevant cancers such as prostate cancer

•    Adipose factor genes provide novel targets for treating obesity relevant cancers such as prostate cancer

•    Blocking of stimulatory adipose factors inhibits growth of prostate cancer cells

•    Adiponectin inhibits growth of prostate cancer cells

•    Adipose factor profiling can be useful as biomarkers for various obesity-relevant cancers such as prostate and liver cancer for predicting cancer risk, diagnosing cancer, determining cancer prognosis and evaluating cancer therapy.

The technology has been tested through in vitro studies and is currently being tested in animal models.