In this special episode, we feature Dr. Karen Knudsen, CEO of the American Cancer Society (ACS).  Dr. Knudsen shares with us her career journey into science and the path that led her to her current leadership role at the ACS.  She shares her story of finding the right mentor, asking the right questions, and being open to new opportunities.      Show Notes:  Dr. Karen Knudsen  American Cancer Society Cancer Action Network  Frederick National Laboratory for Cancer Research  Cancer Letter interviews with Dr. Knudsen  NCI Rising Scholars: Cancer Research Seminar Series    Your Turn: Guest Recommendations  TED Talks by Simon Sinek  New York Times Podcast: Hard Fork     TRANSCRIPT [UPBEAT MUSIC}  OLIVER BOGLER:   Hello and welcome to Inside Cancer Careers, a podcast from the National Cancer Institute. I'm your host Oliver Bogler. I work at the NCI, in the Center for Cancer Training.  On Inside Cancer Careers we explore all the different ways that people join the fight against disease and hear their stories.   Today we are talking to Dr. Karen Knudsen, CEO of the American Cancer Society about how curiosity and strategy combine to make progress against disease.     Listen to the end to hear Dr. Knudsen's recommendation and to have chance to take Your Turn.  It's an honor to welcome Dr. Karen Knudsen to the pod. Welcome.  KAREN KNUDSEN: Thank you so much for having me, Dr. Bogler. It is just an honor and a pleasure to be here.  OLIVER: Dr. Knudsen is the Chief Executive Officer of the American Cancer Society and its advocacy affiliate the ACS Cancer Action Network. She was the first woman to hold those positions. Before ACS, she was on faculty, and held leadership positions at Sidney Kimmel Comprehensive Cancer Center at Jefferson Health, including serving as the executive vice president of oncology services, overseeing both care delivery and research. Her research was focused on precision medicine for advanced prostate cancer with a focus on relapse, a significant problem in that disease. And I should mention that Dr. Knudsen also serves on NCI's Board of Scientific Advisors. Dr. Knudsen, I'm always interested in how people find their way to science as a career. What got you started?  KAREN: Yeah, so I actually don't come from a family that's full of physicians or scientists. It's just something that I wish I could understand even in myself. I think I was just naturally curious about science, and followed that path, and it's steered me in the right direction, that curiosity, I think, my whole career.  OLIVER: Your primary interest was in biology. That's what you studied at George Washington University. You moved into molecular biology. That seems natural. People of our generation were drawn to that field. But then cancer, how did you get interested in cancer?  KAREN: Yeah, it was a really interesting journey that I wish I could say was planned, but really wasn't. So in fact, you know, as a child growing up, I had always thought I would go become a physician, because I thought that if you enjoyed science, that that's what you should do. Again, I didn't know any scientists, so I didn't know how to go about becoming a scientist, nor did it honestly even enter my mind. So I went to George Washington. They have a wonderful biology program where you can have a very rich ability to get to know your professors very quickly, you know, starting your sophomore year. So I started interning in a lab, and in that laboratory, they really recognized how much I loved science and nominated me to work at the National Cancer Institute at Frederick for the summer. And so I interned with Dr. Garfinkel at NCI Frederick, and it was at the time that the HIV epidemic was really in its peak, and really, lack of understanding about retroviruses was profound. And so the Garfinkel lab study Ty1, retrotransposition, and it was thought that this was a way for us to understand how HIV worked. And so I was very excited, in retrospect, to get involved in that because I could draw a clear line behind the science and helping someone, which I think was my driver. So after those experiences, and I was using yeast genetics as a model system, which was very exciting at the time, and still is for me --  OLIVER: Yeah?  KAREN: But it is the case that, you know, I decided to make a shift and that what I really loved was science in the way that you can generate breakthroughs that can truly help more people than you could seeing individuals come to your clinic every day. So this led to this going to UCSD and getting my PhD with a focus in molecular biology. I loved yeast genetics, so yeast genetics was what actually brought me to cancer. At the time that I was there was the time that all of the cell cycle genes were being identified, and the way that that happened in part was that mutational analyses or mutational strategies had been performed at in fission yeast, Schizosaccharomyces pombe, and those new mutant lines, which were sensitive to radiation, distributed across the world in different laboratories, and I was given one to work on, Schizosaccharomyces pombe rad1, which was highly radiation sensitive. And so through complementation strategies, I cloned rad1. It is now known to be what now we know is part of the 911 complex for DNA repair. It got me really interested in cell cycle, really interested in checkpoints, and then of course, you started to envision, well, what do you do with this information if your goal is to help someone? And so that linked to cancer, uncontrolled cell growth and cell cycle, it started to really resonate with me, and still right up until the moment that I stepped into my role as CEO of the American Cancer Society have a very active funded lab where a core component of what we did was always cell cycle, and I'm very proud of my trainees and what they were able to discern but that's how I came to cancer was love of science, being in the right place at the right time, and being able to track it to something that I wanted to do, and that's help people.  OLIVER: Fascinating. I mean, it's interesting that you say, you know, when you were younger, you were thinking of being a medical doctor, right? And then experiencing science gave you that other perspective. That's a lot of what we're trying to achieve with this podcast is to help people see all the different ways that you can participate in the cancer community. So was prostate cancer a disease that you were particularly interested in? Was it just a good model or how did that happen?  KAREN: Yeah, great question. So in my doctoral work, it was certainly all about cell cycle, and I loved it, and I loved the intricacy and the logic of cell cycle and cell cycle gone awry in cancer, but for my fellowship, I recognized within myself that I needed to make that next step, the next step toward more of a direct line for helping someone, in other words, translation. And so I thought about that, as I thought about what mentor I would go work for, and so I, you know, I had the benefit of having all these wonderful labs around me in San Diego, and the interview that really resonated with me was with Dr. Web Cavenee, who was also I know your mentor, too. We had a little time to be in each other's labs --  OLIVER: Indeed.  KAREN: -- And boy, what a great, great decision I made. You know, when I sat down in his office, I realized his mind was aligned with mine, which is the reason that we do this. The reason that we do cancer research is we're aligned towards solving for a problem that is a real life human problem, and I loved that. And so when I decided to join Web's lab, that was probably one of the most pivotal decisions I made in my scientific career, and I thought I would be joining his brain tumor group or his rhabdomyosarcoma group. Of course, I knew him from the cell cycle world as being the person who had identified tumor suppressors through studying retinoblastomas and I was very interested in the RB1 gene. And much to my surprise, after I had already agreed to come, he sat me down in his office and said, "Here's the thing, Karen. All of this work is happening right now in the world in breast cancer." And it was at the time that women had really started to demand more, more clinical trials, more research being done in breast cancer. He said we're going to make gains over there, we, the oncology community. He said but the counterfoil to that is prostate. And you know, the population is aging. Prostate cancer is going to become even more, frequently diagnosed, which was already the number one diagnosed cancer of men in the country, not, you know, like number one malignancy. And he said, we've got to do something about it, because we actually don't understand advanced disease. And I thought, well, what do I know about prostate cancer? But the more I started to look into it from the clinical point of view, from the point of view of what is the clinical problem that needs to get solved, it was a lack of understanding of how it is that hormone action drives uncontrolled cell growth in the prostate. Now this starts to resonate with me. It's like, okay, nobody understands -- everybody understands prostate cancer needs testosterone, but nobody knows how to make that link between what testostero ne does, and how cells get the go grow signal. Understanding that the androgen receptor is present in, you know, many tissues, almost every tissue in the body, what's unique about the prostate, that it gets a go grow signal from testosterone. I thought, oh, okay, I'm probably uniquely positioned to figure that out. And so then pulling together all these wonderful nuclear receptor people that were all around me at the time, you know, I had to of course understand androgen receptor and nuclear receptor signaling in order to link that to cell cycle, and so I was able through partnerships and learning with the community around me, able to put together what I think was a pretty unique research program that led to new nodes of opportunity, new understanding of hormone action, but also new nodes of opportunity for treatment in prostate cancer. And then all these years later, you know, co-writing clinical trials using CDK4/6 inhibitors in combination with hormone therapy. Bingo. I mean, it was really -- it just felt like it kind of all came home when that started to happen. It was -- I was in the right place at the right time, but going to Dr. Cavenee's lab was the most important choice I made to get to the path where I am right now.  OLIVER: And I think you highlight a very interesting and important point, which is being able to identify the right question at the right time in the right environment is so critical to finding work that can make impact.  KAREN: Yeah, and I mean, and I think that's -- I'm very proud of my trainees, and it's the thing that we talked about a lot in the lab all the time. You know, every year, we would set aside some time to say all right, here's our body of work. Here's our body of work in the context of the whole environment around us, and there were no sacred cows. And, you know, we'd say like, what are we uniquely positioned to answer that we can do faster and more thoroughly than another lab? Like, why would we want to go into this particular area? And I think that kind of rigor in thinking actually allowed us to shape and change beyond just cell cycle and to add new types of thinking in the lab about the importance of understanding hormonal control of DNA repair, and then ultimately being able to contribute to PARP inhibitors as, you know, breakthrough approvals for prostate cancer because of that work was really meaningful. And it's because we had such a good tie to the clinic. So, you know, we were constantly thinking about what are the clinical problems that we're trying to solve? What are we good at, at modeling? What is better for somebody else to do because it's just not our sweet spot? And then what resources, meaning people and infrastructure, do I need if I'm going to attack this particular scientific problem?  OLIVER: Interesting perspective. Often the kind of research that you did, that I did, is called curiosity-driven research, but I'm hearing from you that it's curiosity plus strategy.  KAREN: Yeah, I think that's right. I think that ultimately, is how I lead the lab. I think that now when I watch my previous trainees that are, you know, now professors and in pharma, I think it's how their mind works, too. And it was really not me saying, here's the strategy. What I loved about it, what I really, really loved about it was being able to sit with my team every year - we do a retreat, right - and sit and think with them about what is the right thing for us, and hearing their view, their points of view. You know, when you get to that go/no-go part on a experiment, a go/no-go part on a project, it's nice to have the divergence of thought, so that you can ultimately come as the head of the lab to make, hopefully the right decision, not that I always make the right ones.  OLIVER: Who does, right? So around 10 years or so ago, you started taking on some leadership roles in the Sidney Kimmel Cancer Center. You've already kind of told us how strategic your approach was to your science, so I can imagine that was a natural step, but what motivated you to take on those kinds of responsibilities?  KAREN: Yeah, so when I left my fellowship, my first faculty appointment was in Cincinnati at the University of Cincinnati School of Medicine, and I was again, right place, right time. You know, all these brilliant minds had been hired in Cincinnati, right out of their fellowship. Everybody was, you know, very excited about having this groundswell of knowledge of cancer, but I also recognized that I needed to stay very current, again, with what was happening in the clinic, so I was very lucky to have a urologist, Bruce Bracken, and a radiation oncologist who kind of took me under their wing and we started to work together in partnership, and we formed this what we called the prostate cancer working group, and that way, I could explain to him the kinds of things we were doing. They were telling me the problems that they had in the clinic, and we set about trying to solve those together. A missing component was medical oncology, and ultimately, that's why I started thinking about going elsewhere, because at the time, it just was not a missing component, and when you study advanced disease, it's very hard not to have a robust GU oncology program right there. I think they have one now, but at the time, it was just kind of missing, so okay. So I was amenable to recruitment, and when Jefferson came calling in Philadelphia, they said we want you to start the process -- we want you to take -- we have all the stuff. We have all the pieces. We have urology, rad onc, med onc. We have a risk clinic, and we have this massive, diverse patient base, and we've got scientists, but we don't have anybody to anchor them all together. Okay, so now you're speaking my language. So they wanted me to come and start the prostate cancer program. So I did that, and I find a lot of personal satisfaction in building teams. I've learned that about myself through the years. And so I put that together for Jefferson. We started a program that became part of our official programs at the NCI through our NCI-designated cancer center, but we also expanded it to the entirety of Philadelphia. So we started a prostate cancer working group that included every prostate cancer researcher or clinician who wanted to that we could find from Temple, from Penn, from Wistar, and we met once a month, and we put together -- we did work, and which was great, and so I loved that. And so then when you start to be that person, people started to ask you to do other things that require team assembly, so probably not known by the external world very much, but I actually served as the first Vice Provost at Jefferson. So my whole goal there was to -- I was charged by the Provost to put together the clinical and the basic research teams. And at that time then, it was also the Deputy Director of the Cancer Center. So ultimately, you know, the institution made a change, asked me to take on the cancer center right on the precipice of this massive expansion that I actually didn't know was going to be planned. Nor did I think anybody really in the know except our new CEO, so we were a three-hospital system in Center City, Philly. We had great science. The prostate cancer group was ticking and humming. It was really phenomenal, and then we had this incredible opportunity to expand because we went from three hospitals wholly owned and operated with a big prostate cancer base to ultimately, by the time I left, 16 hospitals wholly owned and operated. Now it's 18 across two states. And so I had the opportunity to think about how we take all the awesome research that we do, and put that into practice by putting clinical trials out into the community and setting up four different advanced care hubs with clinical trials so that we actually had an opportunity to get breakthroughs, to get the research that was happening in Jefferson and beyond out to people, and I loved that.  OLIVER: Phenomenal. I mean it sounds like yet another opportunity to make more of an impact and an exciting time also to be there. You obtained an MBA. I don't know if that was coincident with this or what the timing there was, but what was the reason for that?  KAREN: So in at Jefferson Health, we were ultimately a 33,000-employee $11-billion company, and I reported to the CEO. And he's a brilliant guy, Steve Klasko. He's absolutely brilliant. And, you know, I, I learned a lot from my C-suite colleagues, but what I saw (one person's opinion) is that as we went and expanded and assumed these community hospital systems that did cancer care, but had not a lot of expertise in clinical trials, and sometimes they were employed, and sometimes they were not employed, sometimes they were happy that Jefferson had come over, and sometimes they were deeply skeptical about what was going to happen, I realized that we were going through this rapid merger and acquisition and doing it, I'm going to call it in an academic medicine kind of way. And I thought to myself, that there must be a better way, and I'm not going to learn it listening to the echo chamber in academic medicine, and so I'm going to go get my MBA. So I sat with my CEO, and I said this is what I'm going to do. And what he said to me, which I think was brilliant, is he said, "Look, go get your MBA. You go do that thing." He said, "But don't -- do not focus on healthcare. In fact, get away from the healthcare people, because if you really want to break some things and make change, you've got to hear from people with external points of view." And it was great advice. So I learned about M&A from people who were bankers and in finance. And, you know, it's an executive MBA program, so you're working with people who are already in a C-suite, or just below the C-suite and want to be, but you learn a lot from each other. I learned so much that I didn't expect to learn about people strategy and managing, you know, human capital, which you don't ever learn about in science, and so that was really valuable to me, but I also realized what an advantage you have as a scientist, because you are -- you don't realize it, but you are trained with a business mindset, right, because when you're running a lab, you're running a business. You have to think about strategic priorities and finances and human and managing people, but you also have a real comfort with hypotheses and a real comfort with being wrong, and a real comfort with using data to guide your decision, which like It shocked me that some people in the business world just like they actually don't know how to statistically analyze data, and they don't lean on it like I do. So if there's one thing I brought to the American Cancer Society is that we are a data-driven organization. If you want me to run in Direction A, you better tell me why B is wrong, and A is the right way to go, and I'm going to ask you for every piece of data to understand that. And so it's like it's very freeing. I actually think that scientists are uniquely positioned to be business people, (one person's opinion).  OLIVER: That's, that's really interesting, that combination of thought processes. We're going to take a quick break. When we come back, we'll talk to Dr. Knudsen about her work at the American Cancer Society.   [insert ad here please]  All right, and we're back. Dr. Knudsen, your move to the American Cancer Society, from academia to the nonprofit world, represents another career pivot. Same question, what motivated you to take this leap?  KAREN: Yeah, if you would have ever asked me if I would do what I'm doing right now sitting here in Center City, Philadelphia, I would say absolutely not. I loved my job. I was the EVP of Oncology Services. I found great satisfaction in taking the clinical teams and delivering the best possible cancer care in every corner that we covered, and also getting the science there, right, and ensuring that our science is addressing the needs of our catchment area and leaving nobody behind, and developing cancer screening strategies to bring out to the community instead of asking them to come to Jefferson, again, using data-driven research solutions. So I loved all of that, and then I got this call to look at the CEO position at the American Cancer Society, and like you and like other cancer leaders, you get these calls kind of regularly, right? But I was very thankful to ACS because I was an ACS grant holder, right? When I needed research as a cancer center director, I had an IRG grant that gave me pilot funds to spawn what were really amazing new ideas from my faculty. So okay, I was appreciative of that. I was also the president of the AACI, the Association of American Cancer Institutes, which is largely an advocacy organization, and that's where the 106 cancer centers in the US hang together every year, link arms and push for common sense policies to help cancer patients. And the ACS had been our partner there too, so I really respected that part of it, but the thing that really got me about ACS was the fact that a lot of our cancer patients were in Center City and came to our safety net hospital in Jefferson. And so the difference in outcome between someone who can come to chemotherapy five days a week, versus someone who can only come three days a week because they don't have transportation, is huge. So this what I call basic blocking and tackling of cancer care, housing, transportation, digital literacy, information about cancer, education of the caregiver, all of that stuff, which I now call Patient Support at ACS, was how we got our patients to care. And so I was very thankful to ACS, because of all these things, but especially patient support. So I got a call from ACS, and they asked me to take on this job, and they told me something I didn't know, even though I'd known about ACS my whole career. What I didn't know is that this 100-plus-year-old organization was actually not at all 100 years-plus. It was brand new, because ACS had been a federated model. It had been multiple separate organizations with many CEOs and multiple strategies and multiple different areas of emphasis across the country, which explained a lot to me. It explained why I was touching and feeling something at ACS in Philadelphia that's very different than someone might touch in DC, or in Los Angeles or in a rural community, because they were truly separate organizations. So what they explained to me is that they had gone through a business transformation, which I considered to be a good word, and they put together these multiple into one, one ACS, and it was legal, it was financial, as one unit, but it was not yet strategic. So now you're speaking my language, right, because now I have an opportunity to take previous teams, meaning the federated models, and put them together in the name of cancer for the greater good, and so I had this series of meetings with the board, because I had no reason to leave Jefferson. I loved what I did. And if I was going to do it, I was not going to be the keep-the-trains-running CEO, I was going to say we're going to have to have a greater impact than we have right now and define that with data and metrics, and really, act where we are uniquely positioned to act and not someone else. So I had a series of meetings with the board   --  OLIVER: Of course.  KAREN: --  I gave them tough talk. Here's what's wonderful. We got to do more of this. And here's some stuff that I don't know it belongs to ACS, and some of that was with research, and some of it was with advocacy, and some of it was with patient support. I had thoughts about how to structure this to make it more impactful across the country in everything that we do. And I didn't realize that that's what they were looking for, but I think they were looking for someone to come in and really be a change agent, and for a positive. It's always been an amazing organization, always, but clearly ready for logarithmic growth in other ways, and so I feel very humbled and honored and absolutely delighted to lead this organization. We have so much more to do, and we do a huge amount of what we do in partnership, including, the NCI even advocating for NCI funds. It's one of the things I can do as a CEO that you, you know, can't do from within the NCI, but we can and we know how important that is. So every day is a good day because I know we're doing good in the world, and I love that.

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