The development of multiple vaccines to help protect people from COVID-19 showed the power of medical research, given the proper funding and united focus and sense of urgency. Yet one of the concerns during the pandemic has been the potential negative impact it had on research for other diseases, including breast cancer, due to redirected priorities and challenges with fundraising.
Despite all the disruptions that occurred in the last year and a half, Dr. Neil Vasan, a medical oncologist at Memorial Sloan Kettering Cancer Center, says there were some really amazing developments, too. Dr. Vasan, a Susan G. Komen grantee, recently spoke with Komen about his work and some of the unexpected developments that have come out of COVID-19.
Q: COVID-19 gripped headlines for the last year and a half and most of the news wasn’t good. What glimmers of optimism for patients with breast cancer came out of the pandemic?
A: We had four new drugs that were FDA-approved in breast cancer within the last year: tucatinib, trastuzumab deruxtecan, and margetuximab, all three for patients with HER2-positive breast cancer, and sacituzumab govitecan for treating triple negative breast cancer. And all of that happened during the time of COVID, which is just remarkable and speaks to the mission-oriented nature of many of the people in our field and the tremendous progress that we’re making against breast cancer.
Q: At the beginning of the pandemic, there was a lot of talk about what impact this was going to have on research and whether resources would be redirected, whether researchers could be in the lab, and if studies and clinical trials could continue. What impact has the pandemic had on your research in particular?
A: The world was halted for maybe two months, and we were not going into labs. So, we had to accomplish our work in different ways. Some of my lab mates started doing research devoted to COVID. The approach I took was there were some types of work I wanted to do that were more computational in nature i.e. computer analysis, where I didn’t need to be in the physical laboratory space. That was an opportunity to take a step back and ask a question a different way. And it really was just a different way of looking at the situation.
I will say that there were some really interesting things that came out of the fact we were all under quarantine. One initiative I started with a colleague in the U.K. was in the field I work on – kinase signaling – and specifically, a molecule called PI 3-kinase, where we have an FDA-approved drug in breast cancer that’s available for patients. All the people in our field were missing conferences, so we organized a worldwide Zoom seminar series that occurs once every two weeks. We have young researchers present their work from all over the world – America, Canada, multiple European countries, Australia, China, etc. And it’s been a really amazing way to hear about all the scientific advances. Many of these talks are unpublished data, data not yet ready for presentations at conferences or “prime time,” but are really exciting and may ultimately lead to new therapies. These conversations never would have happened if COVID hadn’t occurred.
Q: What about patient care? How did COVID change the way you treat patients?
A: There are some real specific changes that happened in those first couple of months when we didn’t really know velocity or the trajectory of what was going to happen. There were times when we would tweak little aspects of a patient’s chemotherapy, to try to minimize their exposure to the hospital system. For instance, if we didn’t have to give a treatment every week, instead if we can give it every two weeks or three weeks, maybe that would be preferable as we were still learning about COVID and when people frankly didn’t want to come in contact with a hospital if they didn’t need to.
There’s also a lot more awareness of patients and how they travel to and from their therapy. In New York City, where I am, a lot of people take the subway. In other places, a lot of people may drive, take public transportation or take an Uber. Things we took for granted before are now coming under scrutiny in the hope that you’re minimizing your exposures to whatever is out there. But our patients are really amazing. They’re getting chemotherapy or other therapies that suppress their immune system and they’re still showing up to every appointment, on time, and braving through the weather. And that’s really inspiring to see. If someone under the duress of cancer therapy is just doing everything they need to be doing in life, we all need to aspire to that ideal.
Q: Can you tell us a little more about your research field?
A: I work in a field of biology called cell signaling. One way I think about cell signaling, you can imagine you have a house that has lots of different rooms with light switches and all those light switches talk to each other in different ways. Some are on and some are off, and if you turn one on, some turn on while others turn off, but there might be some light switches that really are master controllers and control all the light switches in the house. Using this analogy imagine instead that the house is actually the tumor or a cancer. We know about these very important switches, or nodes, and are areas to target. It can be very challenging, not only in targeting a specific light switch, if you will, but also in figuring out are there certain switches that are better to target than others? Or, if you have this amazing drug, is it only going to work on one particular light switch, the one you want to limit and not affect others. Figuring out these constraints is very important in what we do.
What’s been amazing is that when I started my post-doctoral fellowship, drugs to target PI 3-kinase (a light switch) were in Phase III randomized clinical trials in breast cancer. They had a great track record in Phase I and Phase II trials, but we still weren’t sure at that time who were the best patients to use these drugs, because of side effects associated with these drugs.
Some of my work that Susan G. Komen funded was actually pretty provocative. There was this idea that maybe the field had missed certain mutations in a patient’s tumor. It turned out a significant percentage of patients had these “double mutations” that increased the sensitivity of PI 3-kinase inhibitors, not only in a large number of preclinical laboratory models but in patients. We were able to analyze a Phase III clinical trial and show that patients with double mutations in PI3 Kinase responded better to PI 3-kinase inhibitors. This was a real ah-ha moment that not only was this a clinical validation of our hypothesis, but this was something that could help identify patients who might be better candidates for these therapies
That work was published in Science in 2019, and we’re building on that work now. We’re excited there’s a Phase I clinical trial that’s going to be rolling out looking at PI 3-kinase inhibitors in multiple cancer types with double PI 3-kinase mutations, including breast cancer.
Q: Why is investing in this type of research so important?
A: All of this comes back to Susan G. Komen being willing to seek out these interesting ideas and funding high-risk, but potentially high-reward research proposals. They are high risk intrinsically because they’re asking big questions, questions that are new, questions that are not simply replications of past results or a derivative of a drug or a variation on a theme, but questions that are new fields of science or new themes unto themselves. I think that is a very important area of science to fund, especially areas of science that may be too high risk for more traditional funding sources through the government. Susan G. Komen has one of the best track records for this, because many of the studies Susan G. Komen has funded over the decades have resulted in new therapies, new paradigms, or new ways to mitigate side effects in patients, and all of these innovations ultimately reach patients at the end of the day.