Craig Jordan, PHD, Fox Chase Cancer Center, Breast Cancer Center of Excellence Award:

The standard of knowledge is that estrogen is bad for patients with breast cancer. Estrogen is the fuel that really feeds the growth of breast cancers. What we have been studying over the last probably 30 years in my laboratory, we've helped introduce the drug Tamoxifen and now there are aromatase inhibitors. And we've developed the strategies of long term anti-hormonal therapy to starve tumors of their estrogen. And this has been an enormous advance in the therapeutics of breast cancer, an enormous advance that has really resulted in hundreds of thousands of women being alive today. But the consequences of long term therapy is the development of anti-hormonal drug resistance. And what we have found in the laboratory, really about 15 years ago that nobody believed, was that actually when you stop the therapy and you get drug resistance and you put back physiological estrogen - I call it a whiff of estrogen - and this physiological estrogen now kills the cancer cells dramatically. So this is what we are doing with our program. Tumors that would grow with Tamoxifen and now would be simulated to grow with Tamoxifen, we put estrogen in there and the tumors melt away. When the tumors decrease in size and then grow again we take these tumors and put them in a new generation of immune deficient animals to be able to grow them up,?? the Tamoxifen works again. So we can kill resistant cells and resurrect sensitivity to our treatment. The study really is looking at how estrogen kills cancer cells. Can we translate this to the clinic? Can we help women who have no option but to go on chemotherapy? But now we can control some of them. But we can also now use this as a test bed. The question we want to answer over the next 5 years is why don't 100 percent of the patients respond? Why does 70 percent of the patients not respond to the estrogen? We now, when we create our map of the live and death of breast cancer cells and what the resistance is to the estrogen, we now want to marry targeted drugs that from our map we think are the survival signals stopping the estrogen from working, so we want to convert now 30 percent can we make 90 percent of a response by marrying in 2 or 3 other drugs that critically stop the survival of the non-responding cells. So this is really a revolution in being able to think about how to use this targeted therapy estrogen again, this physiological estrogen, to be able to melt away tumors and now marry it with all the wonderful agents that are being developed by the pharmaceutical industry - but we don't know how to use them. We are now going to provide the options of being able to use them to block this pathway or that pathway. Use the estrogen and just collapse it like that.

We have a multi-institutional Center of Excellence Grant headquartered on Fox Chase and sub-contracted to 2 different places. One, Translational Genomics in Arizona and they are doing our genomics, they are finding out what genes are being switched on and switched off in our models centered in Fox Chase. We also have a sub-contractor, Georgetown University, the Lombardi Cancer Center, and they are doing proteomics. All of this information is then really brought together in a secure web for data mining. The Center of Excellence Grant is absolutely unique because it's innovative. It actually takes the idea that you have and says that's a great idea. It doesn't actually make you do it one way or another. It's getting the results in a timed series of experiments that then feeds into the whole. So this is a unique mechanism that has provided us with absolutely the opportunity to be able to integrate laboratory and patient care really way up front.