Svasti Haricharan, PhD, Assistant Professor Department of Tumor Microenvironment and Cancer Immunology at Sanford Burnham Prebys talks about identifying the hormone in breast cancer and how her team works to find the right therapy.
Interview conducted by Ivanhoe Broadcast News in February 2019.
Tell us a little bit about your research and your work helping to identify the hormone for breast cancer.
SVASTI: Right, so breast cancer is a really common disease. It’s one of the most frequently diagnosed cancers in women in not just the US but across the world. And the most common form of breast cancer is estrogen receptor positive which is what 70 percent of women diagnosed with breast cancer get. Although there are therapies available that target the estrogen receptor, and about 60 percent of women would respond to those therapies. We don’t know how to differentiate between the 60 percent of women who will respond and the 40 percent who will not. Because it’s such a common disease that means about 40,000 women die every year in the US alone from breast cancer that does not respond to standard care. These women are just given standard care, and we just watch them to see whether they’re going to respond or not. By the time we find out they’re not going to respond, it’s too late and the cancer has spread and they’re going to die of the disease. What we work on is trying to identify what are early markers that we can look for in these women and say, will this woman respond to standard care or not? If she will not respond to standard care, there are alternative targeted therapies that we can use that will work much better as long as they’re given right off the bat rather than waiting 10 years for the cancer to come back before we give them the targeted therapy. That’s a lot of what the focus of the lab is. We identified one particular protein that when it’s lost or defective in women with breast cancer, they do not respond to standard care. We think that there’s a way to detect this early on, right when the woman is diagnosed with breast cancer.
So is that the only mechanism that would…
SVASTI: We for sure know that it’s not the only mechanism, but we were really lucky to find it because we had the advantage of working with clinicians and collaborators who had patient tumor samples. Instead of looking for things that go wrong in cells in a plate or in a tissue culture or in mice, we could actually look in real human tumors and things that happen in women with breast cancer. And what is different about these women who respond versus the women who don’t respond? Which is how we found the protein that we found. We think that there’s plenty more to find where that came from, and that’s definitely an ongoing focus in our lab.
This line of research of course is going to be life and death for a lot of people, but it absolutely changes the way that breast cancer may be treated in this country.
SVASTI: Absolutely, one of the major issues with the way we treat breast cancer in this country is we actually have thousands of therapeutics that we can give them, and we just don’t know how to match the right therapeutic to the right woman. We’re in this position where we have all this knowledge, and we’re sitting on top of it and we just have these tiny missing pieces. Once we plug those missing pieces in, we should really efficiently be able to match the right therapy to the right woman, and hopefully not have her go through 20 years of therapy you know and just cure the disease right away. That’s obviously the hope.
Not specifically personalized medicine, but definitely on the path to that?
SVASTI: On the path to personalized medicine.
How close are you to testing this on people?
SVASTI: We’re actually pretty close because fortunately, the protein that we found is already detected in other cancer types. In colorectal cancer patients, for example, they routinely look for the presence or absence of this particular protein. The funny thing is even in colorectal cancer they don’t know what to do in patients who lack this protein. They just know that it’s a bad sign, but they don’t know how to treat those patients. We happened to find a targeted therapy that worked really well in a small clinical trial of women with breast cancer who were defective for this protein. And so ee think that drug is already FDA approved. It’s already in the clinic. The diagnostic test for this protein is already FDA approved and in the clinic. It’s just a question of bringing them both together in the context of breast cancer and testing to see if it’s an efficient way of doing things. Some of our clinical collaborators are already working on doing preliminary analysis of human tumors to see if they can use the colorectal diagnostic test in breast cancer patients.
What’s the drug?
SVASTI: The drug is Palbociclib. It’s a CDK inhibitor. It basically stops cells from dividing.
So there already was a trial, but you needed tissue. And then it’ll start with a Phase 1 trial for people if that turns out the direction that you go?
SVASTI: Right. We don’t need a Phase 1 trial because Phase 1 trials have been done with this drug in breast cancer patients actually. But the thing was we knew that a percentage of women responded but we didn’t know why they responded to that drug. It’s the whole missing pieces thing. We knew that 30 percent of women respond to Palbociclib and don’t respond to standard care. We don’t know how to identify those women from the get go. What we’re doing now is we give every woman Palbociclib which has a lot of side effects. But it’s not going to work in a third of those women. Now we think we know how to identify that third of women so the other two-thirds of them need never have this drug that’s never going to work in them. They don’t need it. You find the one-third rate at the beginning, and you give them the right drug instead of trying out different therapies that are never going to work and giving them all sorts of side effects and quality of life issues. You just give them the drug that will work and hopefully in the short term they will respond to the drug and potentially be cured of their disease.
And as you find more proteins there’ll be different drugs and different assays and all those things?
SVASTI: Yes, one of the great things about Sanford Burnham Prebys is they have a drug discovery center. Our lab works with them closely to say as we’re finding new proteins; can we match them to existing FDA-approved drugs that are already being used either for breast cancer or other cancer types? We go back to match the following and see if we can identify the right protein that would be targeted by the right targeted therapy. And then we don’t have to do Phase 1 trials which are just for efficacy and safety of a drug because these are already done for these drugs that we’re testing. And it saves a lot of money. It’s hard to do these clinical trials and it’s hard to get investment from pharmaceutical companies to do these trials. So if we go with drugs that have already been tested, we’re halfway home.
We’re seeing that more and more. What haven’t I asked you about the research that you think is important to include?
SVASTI: I think we kind of talked about it. I think the most important thing about research is that we are now in this era of high throughput informatics. We have access to genomic data, proteomic data. With this huge glut of information, we really have all the answers. We don’t need to spend a lot of money repeating these extremely expensive clinical trials and collecting samples. We already have them. It’s a question of accessing them and sort of searching through them to find the important clues that you can then match with the information that we already have. I think the focus now is we have all the information at hand, how can we most intelligently leverage the information to help the most number of women in the shortest amount of time?
So do you have a timeframe to when the next round might start?
SVASTI: So this, for example, the Palbociclib story where we match the drug to the defective protein, we think with our clinician collaborators that within five years that could be a valid therapy that’s available to them and a lot of the diagnostic tests that will be done routinely.
END OF INTERVIEW
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