Patricia S. Steeg, Ph.D.
Patricia S. Steeg, Ph.D., a cancer molecular biologist who discovered the first gene that suppresses cancer metastasis and has explored how tumors manipulate and infiltrate the blood-brain barrier, is announcing her retirement after more than 40 years at the NIH.
Steeg’s long-running affiliation with the NIH began with a collaboration with the late Joost “Joe” Oppenheim, M.D., while she was a doctoral student at the University of Maryland, College Park. After receiving her Ph.D. in 1982, she began a postdoctoral fellowship at the National Institute of Dental Research, where she was a Jane Coffin Childs Memorial Fund for Medical Research Fellow in the Laboratory of Developmental Biology and Anomalies, later moving to the NCI to explore breast cancer metastasis. In 1988, Steeg discovered nm23 (NME), the first identified gene that specifically suppresses tumor metastasis. She later characterized its metastasis-suppressing activity in tumor cells and biochemical functions. Her laboratory focuses on breast cancer metastasis to the brain and central nervous system, as well as identifying and preclinically validating new preventives and therapies to target mechanisms of metastasis.
Steeg earned tenure at the NCI in 1992 and became Deputy Chief of the Women’s Malignancies Branch in 2014. She was elected President of the Metastasis Research Society from 2010 to 2012 and received the American Association for Cancer Research (AACR) - Women in Cancer Research Charlotte Friend Memorial Lectureship in 2020. She also serves as Co-Director of the Office of Translational Resources.
Stanley Lipkowitz, M.D., Ph.D., Chief of the Women’s Malignancies Branch and longtime colleague of Steeg's, says, “Pat is a world-renowned expert on cancer metastasis and has made major contributions to the understanding of breast cancer metastasis, brain metastasis specifically. Along with many others in the lab, she explored challenging projects to unravel pathophysiological mechanisms of breast cancer metastasis and to identify therapeutic targets for the prevention and treatment of brain metastases. She brought her expertise in translational work and preclinical models of brain metastasis to the Women’s Malignancies Branch as a founding member, strengthening the rationale for our investigator-initiated trials. Pat also mentored two tenure-track investigators in our branch and helped them develop their programs. Her lifetime dedication to cancer research will be well-remembered at CCR.”
In the Q&A that follows, Steeg discussed the work she has performed over the years and advice she has for future researchers in the field.
Throughout your career, what scientific achievements are you most proud of?
I've studied tumor metastasis, which is the movement of tumor cells from the primary tumor to other sites of the body, and progressive growth in those sites — how that happens and how we can prevent it or treat it. Most of my work has been in breast cancer.
When I started at the NCI as a postdoc, the field was very phenomenological: you put tumor cells into a mouse and you saw the endpoint of the metastases. But, at the time, there was a lot of debate as to whether there were consistent molecular pathways that regulated metastases, because if you look at metastases, one's different than the other, and if you look within a metastasis, one part of it is different than the other. There's so much instability and heterogeneity that it was really debated.
My first major contribution was that I discovered the first metastasis suppressor gene. This is a gene that typically has reduced expression in highly metastatic tumor cells, as compared to poorly metastatic tumor cells, which just don't move well. When we put the gene back into highly metastatic tumor cells in mice, there was no difference in primary tumor growth but there were significant reductions in metastasis. And what this showed is that metastasis is more than just tumor growth, that there are pathways involved in how tumor cells move and grow in new locations.
My second major contribution has been a shift in my work, starting about 15 years ago after listening to clinical colleagues talk about their patients’ cancer progression, to study brain metastasis of breast cancer. Most of my previous work was in breast cancer metastasis to the bone, the lung and the liver. These were very common sites, but I started hearing about patients getting brain metastatic disease, and this was just shocking. It had happened before, but never to the extent we were hearing about, so I started a cellular and molecular characterization of brain metastasis. Most cancer patients are more afraid of brain metastases than any other site, because this is their neurocognition. It's your sense of self, it's your ability to think and to do the daily chores of living. There may also be physical symptoms, such as seizures.
I realized quickly that we needed mouse model systems to study this. We developed seven of them, which we've shared hundreds of times around the world. Then I realized that this problem was bigger than my lab, and I wrote a Center of Excellence grant to the Department of Defense Congressionally Directed Medical Research Programs Breast Cancer Research Program and brought together 21 investigators to establish this line of research. And that has been a major success of the lab – we have identified pathways that mediate brain metastasis.
We mostly focused on why many chemotherapeutic drugs don't work on brain metastases. They have a certain amount of efficacy for lung, liver and bone lesions, but typically very low efficacy on brain metastases. This is in large part because the brain vascular system is protected by the blood-brain barrier, which keeps unwanted substances out of the brain. When a brain metastasis forms, this blood-brain barrier becomes partially broken down, and we have spent years trying to figure out whether this breakdown is chaotic or if some of the same breakdown processes are happening in many tumors.
The answer is yes, there are: the modified blood-brain barrier, which we call a blood-tumor barrier, shows a panel of specific alterations in many mouse and human tumors, and some of these alterations actually mediate its altered permeability. We’re trying to find ways to get drugs through that new blood-tumor barrier and hopefully improve their effectiveness.
We have also launched a first-in-human clinical trial to prevent certain kinds of brain metastases and my collaborator, Alexandra Zimmer, M.D., M.Sc., who was at NCI and is now at the Oregon Health & Science University, is going to continue with that work.
Do you have any advice for those starting their career here in CCR? What advice do you have for future generations of cancer researchers/physicians?
I was advised as a graduate student to know the literature, identify the two or three most important questions in my field, and go after that. Because you can spend 10 hours a day working on a low priority science project to give you one more minor paper, or you could spend that same 10 hours a day on the most important questions in your field: the latter is going to advance the field and potentially your career much more.
Another piece of advice is not to expect people to read your mind and to speak up for what you need. If you are going to sit back and wait for your supervisor to figure out what you need, it may or may not happen. But if you can respectfully say, “I need help with this,” there's a good chance you'll get it.
Finally, for Ph.D. students, learn from your M.D. colleagues. If you ever want to move your work into the clinic you have to know what cancer histology the work applies to, what the standard of care is, how your findings fit in, and how clinical trials are planned and performed. Otherwise, you will spend your time spinning in circles.
What are you looking forward to most in your retirement?
I'm heading to Mexico the day after I retire, and I'm spending time in Greece. I'm also hoping to spend some time on my outdoor hobbies – I’m an avid gardener and naturalist – and spend more time with my grandchildren. I’m volunteering with the Montgomery County school system to mentor STEM teachers.
I'm coming back as an NIH emeritus faculty, and I still hope to contribute to the drug development process in the Office of Translational Resources. You’ve got to believe in the mission, it's for a very worthwhile purpose.
Dr. Patricia S. Steeg will retire from CCR on February 28, 2025.