I have been fascinated with cancer research since I was little. I was raised during a generation where cancer was no longer being thought of as a taboo conversational topic, but rather understood as a mechanism of disease that must be addressed. My research goal is to be part of the dedicated researchers and physicians working to cure cancer. As I am transitioning from being a student to a scientist, it is clear that this is a lofty goal. However, even lofty goals can become reasonable when subdivided into smaller, more attainable objectives such as understanding the differences between normal and cancer prostate cells. Understanding these differences is important because the ideal therapeutic drug targets and kills only the cancer cells and is not toxic to the normal cells. With prostate cancer, most people do not die from the initial cancer, but patients die when the cancer metastasizes, i.e., spreads to other parts of the body. Prostate cancer cells depend on androgen (aka testosterone) to live and grow. Androgen affects the cell by binding to the androgen receptor (AR). The most commonly prescribed treatment for metastatic prostate cancer is androgen ablation therapy. Androgen ablation therapy prevents androgen function by inhibiting both the production of androgen and its binding to AR. Although cancer cells will initially respond to treatment, there are some cancer cells that do not need androgen to live. Over time, these cells will continue to live and grow unchecked causing the cancer to spread. Therefore, while androgen ablation therapy can be used to manage advanced disease, it does not cure prostate cancer. However, if you eliminate AR in the prostate cancer cells, even if they do not need androgen to live, the cancer cells die. This suggests that a better target for killing prostate cancer cells would be AR itself, or any proteins that AR effects. It would be better to target the proteins AR effects since this may be different from normal cells and would limit the toxic effects on normal cells. However, it is not understood what proteins AR effects to promote cell survival. My work will identify what proteins AR effects in the normal and prostate cancer cells to see if there is a difference to be exploited so just cancer cells could be targeted during therapy.

Prostate cancer cells are also different from normal cells in how they sense their environment and how they know when to live or die. One way that cells can sense their environment is through proteins called integrins. Integrins allow cells to bind matrix or connective tissue in the body. If cells do not bind matrix, they die. However, how the integrins tell the cells that the cell is attached to matrix and thus the cell should live and not die is not completely understood. We already know that the type of integrins prostate cancer cells use are different from the type of integrins normal prostate cells use, and that the kind of matrix the integrins bind to is different, and it may be that the mechanism by which the integrins tell the cell to keep living (or survive) is also different in these cells. Understanding this difference is important to develop therapeutics against prostate cancer because it would allow us to kill only the tumor cells.

My research goals include trying to identify the differences between normal and cancer prostate cells so that novel therapies can be developed to target and kill only the cancer cells. An important aspect of this training is being able to present and discuss my research with other people in the field of prostate cancer research as well as to see what these other people doing. It may be during these forums that new ideas and collaborations are generated. The training plan will support my interest in pursuing a career in prostate cancer research because it calls for me to be constantly engaged by other scientists in the prostate cancer field. I will meet monthly with other scientists at Van Andel Research Institute who are also studying prostate cancer. Similarly, I meet once a year with other prostate cancer researchers in the region at the Michigan Colloquium on Prostate Cancer Research. Our ongoing collaboration with Dr. Beatrice Knudsen of the Fred Hutchison Cancer Research Center provides opportunities to discuss both normal prostate and prostate cancer biology as it is observed in the clinic. I will also attend national conferences annually that are directed toward cancer in general. The proposed research plan will support my interest in pursuing prostate cancer research during my career by developing a solid foundation in both normal and cancer prostate biology as well as helping me to develop important laboratory techniques that will be critical in my career as a cancer biologist.