Future AACR President Discusses Leadership Goals, Advancing Cancer Research and Precision Medicine

Nancy E. Davidson has been elected as the AACR president-elect for 2015-2016 and will be assuming the role of president in April 2016. As the director of the University of Pittsburgh Cancer Institute and UPMC Cancer Center, a medical oncologist, and a physician-scientist with a focus on clinical and translational breast cancer research, Davidson is involved in nearly every step of cancer research from the lab to the clinic.

Davidson discusses her leadership plans for the AACR, as well as precision medicine in oncology, challenges with research funding, and the role of epigenetics in breast cancer.

What do you hope to accomplish as AACR president?

The AACR has been in existence since 1907. It is probably one of the oldest of the cancer-related professional societies in the world. This is an organization with long-standing goals, and I think the purpose of a volunteer president like myself is to continue to push for those goals.

What the AACR emphasizes, and what I will also, is to create new knowledge about cancer and to advance human health. We want to make sure that we are doing everything possible to give our members the advantages they need to accomplish their professional goals. Our members can’t accomplish those goals if there are no resources. There is a lot of emphasis right now on trying to maintain, and hopefully advance, our research funding in this country. That will be a big mission for us.

We are also putting effort into thinking about our workforce, and making sure that people are still coming to work in this field. Cancer, despite our best efforts, is not going away anytime soon. We need to make sure that we have the next generation of individuals who are passionate about cancer research and are productive.

Lastly, I am a physician-scientist by training, so I do want to make sure we think of the entire spectrum of cancer research. This includes the most basic discoveries, all the way through to how we take insights about cancer and disperse them into the community.

What do you see as the primary barrier to the continued advancement of cancer research today?

The biggest challenge in cancer research that is different from a decade ago is the resource problem. Now is a time when our momentum has never been higher. There are so many opportunities to apply what we are learning about normal and malignant cells and panomics, which are genomics, proteomics and transcriptomics. Scientifically, we have this giant opportunity and momentum; unfortunately, it is paired with a time of great economic stress. That is different from a decade ago.

The National Institutes of Health doubled the budget for research between 1998 and 2003. This was an opportunity for a lot of people to come into the field, for new projects to start up, and for new ideas to emerge. However, it came to a screeching halt after that build-up. This is a huge problem. There is a real mismatch between scientific opportunity and resources.

How do we go about changing that?

We, as a country, need to come to grips with the fact that biomedical research needs to be a huge part of our investment going forward. It should be through federal means and with support from corporate America. We need to link all of those potential allies and think about how we can effectively provide resources going forward.

Outside of funding challenges, what recent changes have been most significant in terms of understanding the treatment of cancer and what is on the horizon?

In the last decade, we have developed a deeper understanding that cancer is not a handful of diseases, but instead a large number of diseases. With something like lung cancer or breast cancer, there are so many different molecular subtypes that come under the umbrella of breast or lung cancer but are very different biologically. They have different implications in terms of the natural history of the disease, and they certainly have different implications in terms of treatment. This has caused the whole initiative toward precision medicine, which President Obama accelerated earlier this year. I think that was inspired in part by the experience in cancer research, where we have been able to decipher so many different subtypes.

Has any of your research focused on precision medicine?

Early on in my training, I was fortunate to land a summer job in a breast cancer lab around the time we were beginning to understand some of the science behind the estrogen receptor and estrogen response mechanisms in breast cancer. That is kind of the poster child for precision medicine. These are pathways that we can identify and understand, and that we have been able to effectively target for several decades now. My interest remains in that area. I’ve had a lot of interest in estrogen response and hormone resistance in breast cancer.

More recently, I’ve been interested in the epigenetics of breast cancer, and whether epigenetic mechanisms play a role in the development of the disease.

Can you further explain the role of epigenetics in breast cancer?

Much of what makes us up is our DNA. Sometimes, in a disease like cancer, you can have mutations in the DNA sequence. It turns out that not all changes in cancer are caused by a change in the DNA sequence. Epigenetic changes could involve changes in proteins called histones, or might involve other kinds of changes that lead to a subtle modification in some of the DNA. This can also change how the DNA is read out into RNA, and ultimately translated into protein. These are other ways you may see alterations in transcription pathways.

Epigenetic changes can also work in tandem with genetic changes, so both changes lead to the development of the cancer in this case. The beauty of epigenetic changes is that they are reversible. If you have a mutation in your DNA, it is hard for us to fix that; however, if you have epigenetic changes, it may be possible to reverse them. It has been very interesting for us to think about how these changes come about and if there are ways we can overcome them.

What therapies could be used to potentially reverse these epigenetic changes?

There are drugs in development that could do this, and there are some that are actually already being used for various types of malignancies. For example, DNA methyltransferase inhibitors are already being used to treat certain types of leukemias, and there is also a group of drugs called histone deacetylase inhibitors.

These are already used in clinical practice, largely for hematologic malignancies, but we are wondering if these could also work for breast cancer, colon cancer, and other similar cancers. We are exploring these possibilities in the context of breast cancer. Currently, we are in the early stages and have done some early clinical trials and know that we probably need to go back to the laboratory for a while. That is an area I have been especially focused on for the last decade or so.

Is there a specific type of breast cancer patient that you see these therapies being most effective for?

We don’t know yet; we have done a couple of trials. One of them that we completed not too long ago and has been reported at meetings but not yet published, looks at using two of these types of drugs for patients with advanced breast cancer. The results of that trial are being sorted out.

We did do a trial on the other end that took histone deacetylase inhibitors and asked women who had just been diagnosed with early breast cancer if they would be willing to take one of those drugs for just a few days. Once their tumor was removed, part of it was used for research purposes to see whether or not changes in the tumor were what was expected, based on our laboratory models. We were able to demonstrate that vorinostat did decrease the expression of genes related to cell proliferation and cell growth. We thought that was an early signal that breast cancers could potentially have a response to these sorts of therapies.

Because of this trial, we are now back in the laboratory, mainly trying to think about what this is going to look like moving forward. There are people who are testing some of these approaches in major clinical trials, as well. There is a large ongoing clinical trial examining one histone deacetylase inhibitor partnered with hormone therapy for breast cancer, to see if it will amplify the benefits of hormone therapy. It is not a trial I am involved in, but one that I am cheering for.

With such a high level of dedication, are you able to find time for anything outside of work?

I travel and I read. I live in Pittsburgh, so I am a big professional sports fan and I am passionate about the Steelers and the Penguins. I serve on the board of trustees for a conservatory here in town. Also, I am a big gardener. I like to keep busy.