Eric A. Ariazi, PHD - Fox Chase Cancer Center Breast Cancer Center of Excellence Award:

I'm a staff scientist at Fox Chase Cancer Center and I work in a laboratory of Dr. V. Craig Jordan and Dr. Craig Jordan is the Principal Investigator on a Center of Excellence Grant awarded from the DoD Breast Cancer Research Program.

The primary goal of the Center of Excellence is to investigate how estrogen causes death in breast cancer cells and then to learn how to exploit this as a new therapeutic in breast cancer. So, if I could just illustrate on some of these graphs, what we found is when resistance to anti-hormones develops, that not only is it just one type of resistance but many types of resistance actually evolve over long-term selective pressure of anti-estrogens, we found that anti-estrogen resistant or anti-hormone resistant tumors not only are they stimulated to grow by Reloxafene or Tamoxifen or an Aromatase inhibitor that we've actually found that early stages estrogen also causes growth of those resistant tumors but in late stages what we call Phase II as opposed to the Phase I that estrogen now inhibits the growth of those tumors. And, actually, we found estrogen causes death in those cells that have evolved to this Phase II type resistance. So, we are now starting a clinical trial in which we are enrolling patients that have responded and then failed to two lines of anti-hormone therapy. Perhaps they responded to Tamoxifen and then failed and then responded to an AI then failed and we would term those patients as Phase II resistant. Our whole hypothesis is that we can now treat those patients with short-term low dose estrogen to cause death of all of those Phase II anti-hormone resistance cells. Once all of those Phase II resistance cells are dead, the only cells left behind are the ones that now are resensitized to anti-hormones. So, in our trial, these patients who have failed and responded to two lines of anti-hormone therapy will be put on short-term low-dose estrogen to clear out of those Phase II resistant cells and then put then back on Aromatase inhibitor to re-control their tumors. So, in a manner, this is a very cyclable way to treat the breast cancer patient almost analogous to how patients are treated with diabetes. It now becomes a disease that can be treated and maintained so that the patient can live on.

Without the Center of Excellence, this kind of research cannot succeed. This is a new biology of estrogen action and it is extremely complicated. It is not a one-gene type of scenario. It is many, many genes and the only way that we could succeed in doing this research is tapping into individuals at other institutions that have expertise in specific areas. We have the expertise in the biology underpinning estrogen-induced death. They have expertise in various technologies that allow us to elucidate how estrogen causes the death. And, by understanding the mechanism, perhaps we can find a new target to more specific profile patients that would respond best to estrogen therapy.

The DoD provides a unique mechanism where we can go into a multi-institutional mode. Our previous grants were really multiple investigators within a single institution and so you're limited to the expertise in that single institution. While that can be very good, the best way to combat this is to look for the best talent on a national level. And, that is what the DoD does.