Today I am speaking with Dr. Mark Rubin, vice chair for experimental pathology and director of the Translational Research Laboratory Services. Mark has recently been named director of our newly established Institute for Precision Medicine at Weill Cornell and NewYork-Prebysterian. Mark is going to lead efforts to provide optimal, targeted, individualized treatments that are based on a patient's own genetic profile. A renowned pathologist and prostate cancer expert, Mark uses whole genome sequencing in his own laboratory to investigate DNA mutations that lead to disease with a particular focus on prostate cancer.
LAURIE H. GLIMCHER: Precision medicine is a term that's widely used, but isn't always well understood. So, what does precision medicine mean to you and how will it change the paradigm for patient care?
MARK RUBIN: Precision medicine is a relatively new concept, but the idea is, I think, quite well known to medicine. The idea that we're going to look for very specific alterations or mutations that are seen in individuals' tumor and target therapy so that it really caters to that one specific case.
The Institute for Precision Medicine will be an institute that will be focused on taking individual patients and identifying a targeted therapy for those patients, hopefully identifying a new way of treating them where it might not fit into the standard protocol. And the approach will be to use next generation sequencing. We'll interrogate or look at the entire genome and try to understand what alterations they have, which may never have been seen before and will allow us insight into how we potentially can treat them.
There's also another area, which is that once somebody has failed standard therapy there's not too much to do. That may represent an opportunity to look for why that patient failed, so that when somebody is failing a drug, can we interrogate their genome using next generation sequencing and identify what has occurred that now allows their tumor cells to grow, and can we inhibit them at that point. So, that would be an exciting way that we can use the Institute for Precision Medicine to now offer a second chance for somebody who has failed a common therapy that is just not working.
GLIMCHER: There have been so many technological advances. I feel like we can now attack human diseases in a way that we never could before. And one of those advances has been whole genome sequencing. How has this study of the genome, in your mind, revolutionized the study of metastatic prostate cancer? How long does it take to sequence a genome and apply these insights to the patient?
RUBIN: You can sequence a whole genome in really a few days. Something that took years a decade ago. So that's very exciting. I think that the insights that we're gaining are really at the very, very beginning because as we start sequencing — going from a 100 genomes to a 1,000 and then to many thousand genomes — we're going to start to understand what are the recurrent alterations that, perhaps, are targetable, so we will be identifying new drugs that we'll be able to target disease. The basis for all this work is the basis for all types of clinical work. We have to make the observations clinically to understand which are the patients that are probably going to most benefit from the sequencing initially and then, as we learn over time, I think we're going to see that some patients will really need the sequencing first to understand, because they have some unusual alteration.
GLIMCHER: If you had to guess, how long do you think it will take to actually translate this from bench to bedside, where this will actually impact the care of men with prostate cancer?
RUBIN: I think the translation to clinical practice will occur very rapidly, and that's because there are a number of settings where, if an individual is being treated for aggressive prostate cancer and they fail their treatment, we need to identify what is the next best target. And that is going to be the exact scenario where we are going to be needing to perform whole genome sequencing or some type of sequencing for that informed next step. So, I think it's going to be probably within the next year we'll start that process. And what's really encouraging is that in the Stand Up to Cancer Prostate Cancer Foundation grant that we have in collaboration with several other leading institutions — what's exciting is, is that we're going to be doing that in real-time for men with advanced cancers. So we'll learn about why they are responding and we'll learn also, importantly, about why they are not responding.
GLIMCHER: Here at Weill Cornell, there's been a growing focus on team science, and I think that focus has been growing since Lew Cantley arrived. How important do you think collaboration is to fostering breakthroughs?
RUBIN: The team science element is absolutely critical. It allows this handoff from discovery all the way to clinical implementation to occur much more rapidly. But I think more importantly, we have a whole team talking together. And the fact that everyone is talking and learning — we understand what may be a limitation to one lab is something that another lab can readily do. And we have one of the groups is in the United Kingdom, so it's an international collaboration. Just in our short interactions with Lew Cantley since his arrival, we've recognized that work that he's done in his Stand Up to Cancer grant focused on breast cancer has actually impacted our Stand Up to Cancer grant in prostate cancer. So one of the combination trials that was identified there is now being applied in prostate cancer. These are the types of communications through team science that are absolutely critical to make advances.
GLIMCHER: So, you were one of the first to start looking at junk DNA. It's long been thought, of course, to be just that — junk. But now studies from the ENCODE group and others have shown there are interesting regulatory regions that can affect gene expression in some way or another. Tell me a little about that.
RUBIN: We're in an extremely exciting phase of research because now we're decoding all of what the cells are, all of the messages that are coming through cells. We've almost completely ignored the mutations that are occurring in these areas. This is an opportune time to take the sequencing data that allows us to look at the whole genome and ask the question, 'What is occurring in these areas that we should focus on?'
GLIMCHER: You were at Harvard Medical School for several years before you came here about five years ago. What led you to make that choice?
RUBIN: We have such a great opportunity to take advantage of very active clinical setting where we have patients who are coming in just for their well health check-up, as well as patients are coming in to be treated for cancer and other diseases. That allows us, I think, really, to address a wide spectrum of diseases at different stages. So, I think, that was very exciting. The other very important point is that, this was an institution that was building up. I thought this would be a great environment for us to move the lab and really develop, in my hometown, what I think is going to be very exciting opportunity to make inroads into prostate cancer and other cancers.
GLIMCHER: I always like to hear the background story. What led you to become a physician-scientist?
RUBIN: I grew up in New York City and from a family of doctors, there's not too much thinking going into what you do ... [Glimcher laughs] more of what specialty.
GLIMCHER: I know what that feels like.
RUBIN: [Rubin laughs] More what sub-specialty you would take.
GLIMCHER: Well, I'm very excited about the future of cancer at Weill Cornell and I'm really happy that you're here and going to help us drive precision medicine in prostate cancer and other diseases. So thank you for talking with me.
RUBIN: OK, thank you very much.