In 2011, approximately 33,720 American men will die of prostate cancer. Clearly, there is an urgent need for new treatment options, as well as new methods for selecting the right treatment for each patient, and new ways to determine quickly if a patient is going to thrive after therapy, or if he will eventually succumb to disease relapse. Non-invasive imaging methods, in particular positron emission tomography (PET) which is now widely used in clinical oncology, are especially valuable because they avoid difficult and often expensive procedures that require direct manipulation of the cancer in the prostate. Because cancer is difficult to cure, the chance of success can be higher when patients are given two or more anti-cancer agents at the same time. However, this approach has not worked (well) for prostate cancer patients. We suggest a new approach for treating prostate cancer patients, because we believe two commonly used anti-cancer drugs (one that restricts tumor blood supply, and one that inhibits cancer cell growth) interfere with each other when given simultaneously. We believe this problem can be solved, and a new and better treatment found, simply by giving the two drugs one after the other (i.e., sequentially). We predict that this approach will do a much better job in killing prostate cancer cells (without killing non-cancerous cells). The experiments in our proposal will test this idea in mice. To make our studies more efficient, we have developed new ways to image cancer growth with PET, which will be used to determine whether our new therapy succeeds or fails in each individual tumor-bearing mouse. Thus, we feel we can make a unique and important contribution which can lead to better treatment options for prostate cancer patients. To test our hypothesis in small animal tumor models, we will first optimize the chemistry and select the best imaging agent and tumor model for subsequent experiments. Next, we will determine whether treatment shrinks or stops growth of prostate cancer cells injected under the mouse skin. Then, we will determine whether treatment shrinks or stops growth of prostate cancer cells injected into the bone of mice. These experiments are critical, because they address the most common and most serious scenario in human prostate cancer, when aggressive late stage prostate cancer invades human bone. This is known as metastatic prostate cancer and is lethal. In the last part of our study, we will compare cancer growth and measure treatment success when two anti-cancer drugs are given sequentially or concurrently. Non-invasive imaging will be used before, during and after treatment. Tissue samples will also be examined directly under the microscope, to confirm the results obtain by non-invasive imaging. If successful, this work will provide information that can be immediately applied to guide future clinical trials in prostate cancer, which can quickly lead t a paradigm shift in prostate cancer patient management. The same approach and our novel imaging agents can also help patients with other solid tumor types.

Public Health Relevance

The proposed work will test a new combination therapy strategy for treating metastatic prostate cancer. If successful, this work will provide critical information that can be immediately applied to guide future clinical trials in prostate cancer, which can quickly lead to a paradigm shift in prostate cancer patient management. Similar therapeutic approach, as well as the novel imaging agents developed here, can also be applicable to many other solid tumors.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Medical Imaging Study Section (MEDI)
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Menkens, Anne E
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University of Wisconsin Madison
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