Fighting Cancer with Breakthrough Technology

Peter Kuhn, a founding member of the USC Michelson Center for Convergent Biosciences, discusses breakthrough technology in the fight against cancer in the latest Dornsife Dialogues. Kuhn serves on President Biden's "cancer moonshot" initiative which is working to reduce the national death rate from cancer by 50%.
 
In this discussion with distinguished cancer researcher Amy Ross PhD ‘86, Kuhn shares the latest science and the future of early breast cancer detection using a simple blood draw. The simplicity of the blood draw with the sophistication of today’s understanding of breast cancer through advanced mathematics can bring confidence to the 70 million women in the U.S. who are at risk of breast cancer. 

Learn how USC Dornsife is making a difference in the fight against cancer with:

Peter Kuhn, Dean’s Professor of Biological Sciences, USC Dornsife and cancer physicist. Learn more about his work.

Amy A. Ross PhD '86, cancer researcher (ret.), USC Board of Trustees member

Learn more about the Dornsife Dialogues and sign up for the next live event here.

Transcript

Dean Amber Miller:  Hello and welcome back to our Dornsife dialogs for the fall of 2023. Our topic today has to do with a breakthrough, a new tool for cancer screening that's being developed right here at USC Dornsife. Most of us have experienced some kind of cancer screening, and the rest of us have probably been through this with a loved one.
 
 This excruciating process is often invasive and uncomfortable and generally involves several days of anxious waiting before results are available. The dream of being able to replace traditional cancer screenings with a simple blood draw capable of providing accurate real time information is so powerful that it underpin the Theranos scandal that rocked Silicon Valley. But here at USC, Dornsife dance, professor Peter Coon and his team have developed a liquid biopsy that may finally realize the dream of revolutionizing cancer screening and treatment monitoring.
 
 Professor Koon, the head of USC's Convergent Science Institute in Cancer, has published more than 200 peer reviewed scientific articles, and he's received several patents as a result of his research. His pioneering efforts in the intersection of biology and physics have earned him countless awards and accolades, including a spot on President Biden's cancer moonshot team. Dr. Koon will be in conversation today with Dr. Amy Ross.
 
 Dr. Ross is an experimental pathologist with a distinguished background in cancer diagnosis. She spent her career developing clinical trials and tests aimed at unlocking the mysteries of cancer and other diseases. Dr. Ross has authored more than 75 scientific publications and holds three U.S. patents. She serves on the USC Board of Trustees and her dedication to the university and our alumni community spans decades.
 
 She is also herself a proud USC alumna, having earned her Ph.D. from the Keck School of Medicine. I will now turn it over to Dr. Ross to get us started. And thank you all, as always, for tuning in.
 
 Amy Ross: Thank you so much, Dean Miller, for that very warm welcome and a very warm Trojan Welcome to all of you joining us today on this webinar. You know, I think it's safe to say that each and every one of us has probably been impacted on our lives in cancer by one way or another. It may not be you directly. It may be a spouse, a significant other, a parent, sibling, friend, God forbid, a child. But one of the things that I think can draw us together is our dedication to having innovation and real time and improvement in this field.
 
 So that's why I am so pleased to be the host today and to introduce you to my dear friend and renowned researcher, Dr. Peter Kuhn. You've heard all of his accomplishments were wonderful. So Peter, welcome. Today, I know that you're going to have some wonderful insights for us, so to get started. You know, I think when a lot of people think about cancer, we think of it as this kind of homogeneous disease.
 
 But in actuality, your research and the research of so many others at USC has shown that it's anything but. The cancer is really a number of different diseases, and each of which can have a different cause and a different outcome. So to get us started here, Peter, can you please give us a brief overview of how cancer arises in our body and for example, how a diagnosis of breast cancer can vary so much from person to person in terms of detection, prognosis and outcome?
 
 Peter Kuhn:  Yeah. Thank you, Amy. It is, of course, exciting to be here today and having the opportunity to have this conversation with you. We have had this conversation many times, of course, ever since I started, and you shepherded me along in my Trojan career here. But having it actually in this public setting actually is quite this is actually really quite special today.
 
 So thank you. And you're right. Cancer is not just one disease, but it's and it's many different diseases and it affects different people also very differently. So we have to be thoughtful around when we talk about cancer to be specific enough to be relevant for the individual patient. Most of what we will talk about today is, of course, in the setting of breast cancer.
 
 We'll I'm sure we'll have other dialogs in the future that will touch on other cancers as well. But today, let's focus on breast cancer, because it starts framing the question out that that you stated and that is what are the different types and how does it affect us the way we are being diagnosed. So, of course, breast cancer comes in a couple of different types that some of us have heard about and that have to do with how they occur and the shape within which that they occur.
 
 So we call some of them lobular carcinomas and the other stuff can carcinomas. Then when it comes to treatment, we often talk about hormone receptor positive breast cancer or HER2 positive breast cancer or triple negative breast cancer. All of these descriptions have to do with, again, how the cancer evolves in our body, how it reflects itself, and how oftentimes also how aggressive it is.
 
 And with that, it starts guiding the way we want to treat that cancer. So much of that, however, comes back to a very, very, very basic tenet. And that is the earlier we can diagnose breast cancer, the more definitive we can actually intervene, the better we can use treatments that we really approach that cancer with a treatment for curative intent.
 
 We won't know for sure, but we also have now methods with which we can actually follow a patient who has been previously diagnosed to make sure that the cancer actually stays away. So all of that complexity, I think cancer research over the past, over the past decade in particular has gotten us to a place where we understand it so much better, so much better at the broader at the bigger picture, but also so much better for the individual patient.
 
 And that cancer research is, of course, continuously being translated into applicability to really, really get out into the community for patient care on a daily basis.
 
 Amy Ross:  Thank you. That's a very important point. And I'd like to also follow up by one of the aspects of what Dean Miller was talking about. What makes, I think, USC so unique in our approach to this, as I alluded to, is that we have not only researchers like yourself this very unique Michelson Center for Conversion Bioscience, where we can bring together researchers in cancer biology, in engineering, even students, very innovative students and faculty at our iodine young Academy.
 
 And I think it's taking this multidisciplinary approach that makes this research so unique and also why it is bearing so many results. So with that in mind, you've given us a very good overview of kind of what cancer is, breast cancer in particular, and how it can vary. So let's zoom in now on your research in particular. So can you give us an overview of your approach to cancer research and why detection and monitoring of these so-called circulating tumor cells or ctcs is so critical to diagnosing and treating breast cancer?
 
 Peter Kuhn: Yeah. Thank you, Amy. And so maybe by first, a quick disclosure. In fact, I am not a medical doctor. I have actually no training in medicine whatsoever. I'm merely a physicist. So I am approaching cancer through a very, very different lens than, for example, a biologist would or a clinician would. In isolation, however, I can't make any progress.

But together, in this context of convergence science, the way we approach it, this at USC and really with others around the country and around the world. I really think we can we can make progress in very different ways. So this simplistic physics type construct is can teach us a lot. So when that cancer first emerges and is confined to the breast, when we find it at that stage, we can actually again go in with curative intent.

And that means surgery followed by a drug treatment that, you know, none of this is ever easy. Right? But one can live with that approach, and that works quite well. The challenge arises really when the cancer starts settling somewhere else in the body. And what we are then faced with is what we call metastatic disease. So disease that has spread to other parts of the body.

At that point, the cancer appears to be incredibly robust, very, very strong and very, very difficult to treat. So we spend a lot of time really thinking our way through how can we actually treat that very late stage of the disease. And that is ongoing research. There is a step in between that we kept asking ourselves this question of like, how do we go from in the breast only to spread throughout the body.

And the somewhat obvious answer is, of course, there has to be cancer cells that travel through the blood. The blood is what provides nutrition to the cancer. So that is how a cancer goes from starting somewhere very small, some or very early. And starting to grow. But it's not just that nutritional supply. Right. But with that, also the cancer can leak all of its particles, its cells and other things into the bloodstream.

Now, there's good news and bad news, right? Because your bloodstream is, of course, your immune system. So for the most part, your immune system just starts taking care of everything that gets spilled into the blood. But eventually, for some patients, unfortunately, that leads to that distance metastasis that spread throughout the body that is then so hard to treat.

So so with that, when we then look at that, we said, all right, that's a problem. It's a real challenge. It's a real problem of cancer. As it evolves, can we flip it into an opportunity? And the opportunity arises, of course, that I can take a blood sample quite easily, quite frequently, if I make the argument that the cancer must be traveling through the blood, it means that I just have to develop methods with which I can see it in the blood.

And we develop these methods by really going in, spreading the blood to blood out on a large glass slide, and then imaging it and looking for normal immune cells and for cancer cells. And it's those cancer cells that cause to spread. But it's the same cancer cells that we can now use to actually diagnose the disease. Again, with that ultimate goal of diagnosing the disease early enough that every patient can be treated with curative intent.

Amy Ross: I think I'm going to go back to a conversation that you and I had several years ago that I think is so important because of the number of people who are with us today. Numerically, there have to be some who are in that stage of I've been diagnosed, I've been successfully treated. Now I'm in a period of watchful waiting.
 
 So as we know, with some of the frontline treatments that are used with breast cancer, in the event that the patient recurs quite often, the chemotherapy that is used to treat the patient initially is no longer effective against metastatic disease. And I remember you're telling me about your research at one time where your test is. You mention putting tumor cells out on a slide.
 
 You could actually show that the proteins on those cells are different from the proteins that the patient may have had in her primary cancer. And that is the issue of why. How can we figure out what those changes are and how can we personally adjust chemotherapy? If you could give us just a couple of minutes, please, of insight into that, because I think it will give so much hope to anybody in our audience who might be in that watchful waiting phase.
 
 Peter Kuhn: Yeah, absolutely. So. So there are there are those two phases, right? There is the watchful waiting phase. And then there is the phase when a recurrence has actually been diagnosed. And now I need to start managing that treatment. And so they are actually we have had a number of breakthroughs over the past couple of years to get us to a place where we can we can measure these changes.
 
 So a subset of patients that will have been diagnosed with hormone receptor positive disease, but when they actually recur, they actually recur as a HER2 patient. Now there's good news and bad news. The bad news is, of course, that we think it's a hormone receptor positive patient, so we need to figure out solve that puzzle. But the good news is actually for her to positive disease, we have a lot of really powerful treatments available today.
 
 Right? We don't luckily, it's not the sixties anymore. Right. The availability of drug treatments is really it's quite striking of what we can actually do for as long as we can actually precisely diagnose the disease at that point in time. So this was a really important step that that we got to to to really have that realization, how this disease can actually change within a particular patient and a different subtype can actually start emerging.
 
 And we know exactly how to treat that prior to that is, of course, this other phase that you just described, Amy, and that is this watchful waiting phase. And and that's that's complicated. And it's complicated for a number of health care system reasons, because we previously showed that imaging is no better than just waiting for symptoms. Well, that might be true from an insurance risk assessment perspective, to say politely.
 
 But from a human perspective, it's awful because it means that you are really restricted to waiting for pain. And every time that something itches and aches in your body. You have to ask yourself the question is that the cancer being back or is it just an ache? That to me is is of course, entirely unacceptable. And we have to get beyond that.
 
 And again, how can we get beyond that if we can do that with with really something as simple as a blood draw, now, we can make a huge amount of progress. So there is a number of groups, ours and a number of other groups around the world that are now really working very, very aggressively on that concept. The reason why this is so hard, just to be clear, the reason why this is so hard is because this is a true this is one of the hardest needle in a haystack problems that one can imagine, because we actually don't know really what the shape of the needle looks like.
 
 We don't know how many of them they are. We barely understand the haystack. So this is, of course, the ultimate problem that the physicists we love that kind of problem. So that's really cool. That's where this is really, really exciting. But we are making real progress in that arena. And the data that is coming out again out of our lab and other labs are giving us real hope that these these blood tests will actually really get us there.
 
 Amy Ross: Thank you for that additional explanation. And that's actually a perfect segue way where we would like to discuss now. So you and your colleagues have developed something that I personally love, the name of the pink test that is used to improve detection and monitoring of patients with breast cancer. But most importantly, not only patients with cancer, but as a way to very early pick up patients who may who go through regular mammography, may have a look.

We've all been through this, maybe a little something suspicious going on. So if you can really educate us as to what the pink test is, how you developed it and its clinical potential.

Peter Kuhn: Yeah. So so the pink test really came about really along the same line of the conversation that we just carried out. We first needed to understand breast cancer in its later stages because that is rare treatment decisions are so very important. We then said, okay, now we need to start understanding this earlier phase as watchful waiting phase. But of course the ultimate goal was always to detect breast cancer early and and we did not know whether or not this was going to work.
 
 But when we think about just how important it is this, right. So for all the women over age 50 on this call, the vast majority of you is going to go to your annual screening mammogram and that mammogram, of course, has two challenges. One is, of course, being squeezed between two metal plates, and that is part number one.
 
 I don't think anybody is looking forward to that. Part number two is, of course, as Dean Miller pointed out, is the uncertainty around the results. It's not just that it takes a long time for the results to come back, but the problem is that screening mammography is only about 85% accurate today. And that means that many of you, for together, you have about a 10% chance every single time that it comes back as a false positive.
 
 So you're getting a notice back saying, hey, come back into the office for a workout. The other part of the problem is that about 10% of all breast cancers are actually being overlooked or being detected too late. So if we take that together, we all of a sudden realized that, wait a minute, does a lot of there's a lot of room for improvement.
 
 So now imagine a day where actually we going from 85% to 99%. What if what if we would have a simple blood test that can actually get us to a place of 99% accuracy where we can reduce the number of letters that have been sent to two women around the country and really around the world about coming back to the office, but really as a false alarm and maybe as important or maybe more importantly, we can help women who have to end up with a diagnosis of lobular carcinoma, which is the second most frequent breast cancer that is typically very hard to detect and is typically detected late with mammography.
 
 So you now put this problem setting into into a world like USC. You have where you have the privilege of working with some just absolutely amazing students and scientists. And the work that we have now done over the past seven, eight years that we have been here has gotten us to a publication to a recent publication where we show exactly that, where we can separate women what we call age matched gender match no known pathology, meaning the average woman over 52 women who had just received a positive diagnosis of breast cancer.
 
 That is something that we call the case control study. Right. And compare those two groups. And we were able to separate those two groups with 98 99% accuracy. That was absolutely striking. That was completely unexpected. We really did not think that we can actually achieve that level of performance of this test. Now, that, of course, has now put everything into hyper speed for us, right?
 
 Because all of a sudden we have to ask ourselves two questions, A, how do we verify this? And so we spent the last eight months with as many critical voices as possible trying to to to sort of attack ourselves and try to figure out is just does this that's just still work itself out. And it's actually all holding up.
 
 We have now actually gone to a place where where we have where we where we have looked at subsets, for example, the lobular carcinomas. And we realized that we can actually detect them as robustly as Dr. Carcinoma. So that is awesome, right? So all of a sudden, right, we have now this environment where it's all about verifying, scaling up and really testing this out in different in different populations and different groups of women to make sure that this is actually robust, but then push forward as fast as we possibly can.
 
 Amy Ross: I think that's very important. And one thing I would also like to couple of things I'd like to say to those watching today, even though we are focusing on breast cancer, is kind of a case study here. Peter's work and so many others, this type of research and what we find out about what these circulating tumor cells can tell us is not unique, just a breast cancer.
 
 Peter, you've done work in prostate cancer. We also see this with colon cancer and lung cancer. So it's any of the so-called solid tumor malignancies where these cells can get out into the bloodstream. So again, even though I don't want everybody to think that this that this technology is applicable only to breast cancer, it really is to all of these other malignancy tests.
 
 And that being said, just the number, the names and the colors that you could give all of these subsequent tests, I'm not going to go there. I would have I would also like to ask before I let you and have a comment here, Peter, to those of you in the audience, I hope we're stimulating you here to come up with some questions either about breast cancer in general or more specifically to what Peter's talked about with his research.
 
 Did you want to make any other comment about other other tumor types that this technology is applicable to?
 
 Peter Kuhn: Yeah, absolutely. There's always this it's this interesting question. Are we detecting cancer or detecting breast cancer and how do we actually how do we separate that? We are we are focusing this work around the development of doping tests, of course, on breast cancer because there are 70 million women in the United States alone who are eligible for breast cancer screening.
 
 And and that's a that's a really big number. A friend of mine said the other day, Peter, you do appreciate that that is 200,000 women per day. So every day that we are late in bringing this test to the clinic, you know, there's 200,000 women potentially missing out. So we are we are pushing this forward as as as fast, but also as diligently as we can, which is, again, a strength, a strength for us within the U.S. environment, of course, because we can pull in groups from around the university to really help us all the way from developing new algorithms.
 
 And that by itself is actually, as is quite beautiful. We are doing that, not necessarily all that Dornsife. We actually doing that with our colleagues over at the Mojave School of Engineering. And in fact we are working with colleagues in economics to to start working with us on behavioral economics. What if, what if once we are out in the community, what do we actually need to do to make sure that we can really reach everybody that we want to reach in the community itself?
 
 So there's a lot of work that we can start pulling together within the university framework that goes far and beyond just the additional clinical trials that we are, of course, building up because we need to again now go into the standard screening group of patients and make sure that we actually achieve the same result. So there's a lot of work that starts coming together in this context of just pink test development, a lot of new research coming out of it.
 
 But we also start really appreciating the complexities and the challenges that we're actually facing because again, doing doing something in a research laboratory is very different from doing this at scale out in the community.
 
 Amy Ross: Exactly. And as you said, you know, putting the time in to make sure that you have a test is not only robust, but as you alluded to, there's nothing worse than getting more frightening when you have a false positive with mammography or a false negative. So I know in developing these tests you want to make sure that the robustness of it and the sensitivity and the specificity is something that will give patients more relief than more worry.
 
 Now, I'd like to delve into hopefully by this point in the webinar, we've got a very sophisticated and educated audience watching us here today. You made a remark earlier, and I know in following some of your research now, you'll get a little esoteric. You mentioned that in addition to these circulating tumor cells that can be out in the blood, that the cells can shed other types of things, other clues that they can give us as to what is really going on and what their potential to do harm is.
 
 So your research recently has focused on these so-called orgasms and that they might be able to give us even additional information than just the circulating tumor cells. So can you fill us in a little bit on what orgasms are, why they're important, and why they might be so key to therapeutic intervention?
 
 Peter Kuhn: Yeah, absolutely. So all of this actually started with a again, a brilliant set of students and a rogue rogue set of experiments. In the past, we really we assumed that all of this messaging that happens in cancer as it spreads through the body was really done by cells. Subsequently, other groups had found fragments of DNA as well of tumor DNA as well.

Another important analyte. What students came across a couple of years back was, in fact, these little particles. They looked almost like cells. They had almost the same size as cells, but they didn't have a nucleus. So the nucleus of a cell is, of course, the blueprint. It's the genome, right? It's the thing that you need to replicate, Right.

Because without a blueprint, I can't make a second copy of that cell. So now these particles that we call on costumes, these particles, they they look and feel almost like cells, except they can't replicate. Okay, that's kind of interesting. But what is it that they can actually do? So there's a group of a few groups around the world that have come across them.

But but what do they really mean in cancer development? And so the striking part here really is found in early breast cancer. And we have looked at a couple of other cancers in the early setting as well, very distinct in breast cancer. They are dominant and exist in virtually every woman with early stage breast cancer and they actually taper off differently as the disease progresses.

We still don't really understand the biology fully, but what we do understand in terms of just the power for the diagnosis is that that is really quite striking because that is what separates women with and without breast cancer. So with that, of course, come sort of two big branches, right? One is to leverage these anchor cells together with the cells.

One by itself is not good enough to leverage to two together to build the best test possible, to test, test to test, validate the tests and clinical trials as we go forward in the appropriate patient populations. And that means in women under the age of 50, women with dense breasts, women of African-American origin, women in different across the health care disparities spectrum, women who have been diagnosed previously, women with other cancers with other boundary conditions.

So there's a lot of these additional clinical trials that we need to go to and test out through. That's one branch. But then, of course, there is the other branch and that is that we need to understand the biology and of these anchor storms in particular, what is it that makes breast cancer special? Well, breast cancer is really hormonally driven, right.

And it typically takes a very, very long time for it to go from a small emerging cancer to something that's big enough to feel. In fact, the age of that cancer, we actually don't really understand it very well because we don't know how to watch that within an individual patient. So there's a lot of research that we have to do as we go forward, because that, of course, will be key to us.

Understand funding, early development and then with that, understand how we best intervene at that early stage as well. So all of this research will not just support the quality and validity of the pink test itself, but that will then subsequently vary in rapid fire order and really start impacting our therapeutic development for women who have been diagnosed.


Amy Ross: Yeah. Thank you. You bring up a lot of points. We're about to go to questions and answers here, and I can see some really good ones are coming in. But one thing to also keep in mind is that when these cancers occur in our body, it's not occurring in a vacuum. And as you alluded to earlier, our immune system is trying to counteract.

But remember, a cancer cell is your own cell. Your body cannot recognize it as foreign because it is part of you. So I was actually at a research group at Norris Cancer Hospital a couple of weeks ago looking into very interesting differences in breast cancer from women of different ethnic origins as to which immune cells which may be responding.

So I think that's an area that is of interest also. So suffice to say that we are looking at a very wide approach, not only the tumor and the patient, but the immune system. So, Peter, are you ready for some questions here? We've got some really good ones coming in.

 Peter Kuhn:Always ready. Yeah. When you see my eyes going slightly left and right, I'm like, Oh, wow. Okay. These are really cool questions. Finally.


Amy Ross: Between the two of us, we can go through and go on here. But we've got a good question here from Susanne. Now, again, we have been focusing today on on breast cancer. But Suzanne's question is, most often when I hear cancer presentations, they seem to be tumor focused and not much related to blood cancer. Can you please also address blood cancer?


Peter Kuhn: Yeah, Happy. Happy to do so. Suzanne. So the there's actually a spectrum, right? So there are the blood cancers, leukemias, lymphomas, all the way through multiple myeloma and then over to what we call the solid tumors to carcinomas. Oftentimes when we talk cancer, that is what we talk about is the carcinomas, the solid tumors. Those represent different fields of research.

And in fact, the blood cancers have made so much progress earlier on because fundamentally, because they're easier to access, because a lot of that early research was was guided by being able to access the blood cancer with a blood sample or with a bone marrow spread. So the drug development there has, as in leaps and bounds ahead of the solid tumors, which is why oftentimes you hear us talk more about the solid tumors, because that is where a lot of research focuses today.

There is of course, there is, of course, benefit as we as we start working across and and and maybe a future Dornsife dialog could be on multiple myeloma, for example, because I think that's another really, really important challenge where we're making real progress.

Amy Ross: Exactly. And with blood cancers, as we see with all of these other solid tumors, they're not it's not homogeneous. You have some cancers, you know, ALS, very aggressive. You have others like CML that you can go your whole life and not even know that you have it. So that's one thing to keep in mind. Also, Princeton has an interesting you know, there is one cancer.

I think that, of course, nobody ever wants a cancer diagnosis, but one that is especially troubling is pancreatic cancer, because of not only is difficulty in terms of detection, but quite often no treatment is available and lifespan is very short. Can you comment, Peter, on any insights you might have into pancreatic research, particularly as it might relate to your approach?

Peter Kuhn: Yeah, I know, absolutely. Preston So within our research portfolio, we actually have a, a really an exciting and again, when I say exciting is because we're getting to results.

We are collaborating with our colleagues across, across the play base. And so this is with our colleagues over at Cedars, and they approached us and they said, Hey Peter, when we do this diagnostic workup in for the suspicion of pancreatic cancer, there's a set of challenges we have. Can you work together? So we started working together over the last three or four years now, and and at the research level.

And these papers will start coming out over the next 6 to 9 months that will actually describe how we can separate pancreatic cancer patients from patients without pancreatic cancer. The work is probably two or three years behind our breast cancer work. The challenge is slightly different because it's less of a screening question than it is a diagnostic question at this point.

And that I think will relate to some of the other other questions as well. So I would say thoughtful, careful research by us and others is making some really critical progress towards being able to diagnose pancreatic cancer earlier than we do today and with much higher accuracy as well.

Amy Ross: Yeah, very important. Thank you. George brings up a good point. You know, Peter and I, you, we have been not only bench scientists in terms of developing this, we've worked in clinical trials. We've also worked with companies in terms of this is really good and really interesting what we've got going in the lab here, but we've got to get it out of the lab and we've got it into practice.

So what George would like to know is how long does it typically take a cancer test like the one you've been describing to get from a research setting to a broad base acceptance and research into the ecology community, including clinical trials?

Peter Kuhn: Yeah, So that's a that's a question that we have been teasing apart over the past six months. We put together a you know, if you think about this as research development and then commercial, right. And the question I think or the way I'm going to answer your question, George, is how do we go from research through development right to that line of commercial?

And to me, that line is having regulatory approval, having FDA approval. So this development phase, we are actually now put under the umbrella of what we call U.S. Intercept, and that is is 100% dedicated to the next steps that are required to getting us FDA approval, in fact, doing the Cancer Moonshot, its first iteration in 2016, we started working together with partners around the country, everybody interested commercially as well as academically, as well as from the regulatory perspective into advancing these liquid biopsies.

And so we work very, very closely with the FDA to really understand the trials need to be conducted to get us there in this particular setting. And the answer to your question really depends on the setting. So this is a breast cancer specific test, which means that in the clinical trials that then we will start these negotiations where the discussions with the agency over the next couple of months.


But in this particular setting we have to demonstrate that we can outperform screening mammography as good as or better than screening mammography. That's a very specific trial target. That trial we can design and execute. So we should be getting we should be able to get through that trial phase fairly quickly. Prior to that. The test needs to go from what we call research use only into a compliance laboratory developed test environment.

So that's just another hurdle that has to be overcome so that we can ensure and demonstrate reproducibility. So all in all, we're talking a couple of years until we we are really there at the approval stage. But trust me when I say we, all of us within that U.S. intercept framework are incredibly impatient for for those of us who have who are married to women that we dearly love are on our backs.

Because, again, there is I don't there's no time to lose. But we also have to recognize that the regulatory requirements are actually really important to fulfill, right? Because we have to generate the evidence that this really does what it is supposed to do. And so so that's why we are engaging with the agency early on to really make sure that we're putting us on the track to success.

Amy Ross: Right. And I think also something to keep in mind is that for FDA or even CE mark approval in Europe for, a test such as this, the FDA has a different pathway for getting a medical device or a test to prove than it does a drug. So the timelines can be shortened a little bit. But again, there are obstacles that you have to go through.

It takes time. It takes money. You know, bringing a test like this to market with everything. As you mentioned, Peter, from clinical trials, working with FDA really does take a lot. And we did actually have a question about that kind of follow up. You mentioned timing of mammography. So what Diane is asking, A, where can patients get the pain test?

And is it the same because are there clinical trials with pink does or how would somebody watching today go about being part of this exciting research.

Peter Kuhn: Yeah. So we are in the middle of designing the follow on trials. And the follow on trials will be a group of trials. Again, some of the hurdles are purely financial. We have, of course, in the middle of trying to to really raise the money to support that because it's complex of just a number of different groups that need to work together.

Right. Because all of a sudden this is now not in the setting of what we are used to work with, without with our colleagues at the cancer center. We now work actually, you have to work with with our colleagues out in the community centers where women undergo a screening, a screening mammography. So this is exciting. It's a little scary, I have to say.


Right, because we haven't done that before. But again, we have lots of colleagues around us who actually help us shuttle that through. And I would say follow us on, intercept of us on Edu, where we will over the next couple of weeks and months, really update continuously of where we're at. Again, the beauty of doing this within the academic setting is, of course, that we will do this with complete transparency to our community, to the Trojan community, but of course to the entire to the entire public at the outside, these I'm hoping that the first trials will open by the first of the year.

That is probably a reasonably realistic and not overly aggressive target. But I think that's quite that's that's quite feasible.

Amy Ross: Hopefully that will doable. There was one question that came in and we kind of alluded to this. We all know that women with dense breasts, that mammography, it's difficult. We certainly have better radiology now for women with desperate other types of tests, ultrasound and so forth. But the question is, do you think that this type of technology of, you know, detecting tumor cells will be particularly advantageous to women who have dense breasts and quite often can go through difficulty or false negative?

Peter Kuhn: So I'm going to do the evidence based answer first, and then I will go into what I think. So we I mentioned briefly that we pulled out the women who ended up with a diagnosis of lobular carcinoma. It is it is one of those very difficult to detect breast cancers and in particular in the setting of dense breasts.
 
So and and we have the same accuracy as we have with a Dr. Carcinoma carcinomas. So we feel very confident that we can find them. So with that, I'm going to now extend to what I think and we're going to also tell you how are we going to build the evidence around it? What I think is there is no reason as to why a breast cancer would reflect itself differently in the blood.
 
Whether or not a woman has dense breasts, there is no reason to expect that. That's what I think. We have to prove that. And we can only prove that through a clinical trial. And again, to give you a feel for what these clinical trials need to look like is that if you if you take a thousand, a thousand women and, you test them all for breast cancer, five of the 1000 women will have breast cancer.
 
 

So that gives you roughly a feel for the kind of scale we are looking at from a clinical trial perspective and what's ahead of us. So so that's how we are making progress. We are designing these trials. We're going to follow these women from a clinical history perspective and then establish whether or not this 99% accuracy off the test that we saw in our case control study will in fact, hold up in the in the community setting as well.
 
 Amy Ross: I think that's a very important point. And we actually did have a question from David about accuracy of the test. And you say 99%. But again, when you're developing a test and you're looking at optimum situations in terms of development, when you get it out in clinical trial, there's a number of other factors that can intervene. So I think to David, to answer your question, this is one of the things that we do look forward to.

We look at in ongoing clinical trials. When you're dealing with patients with a variety across the spectrum of where they may be. So, no, you brought up a very interesting point. You alluded to working with other institutions, Peter, and and work like this doesn't occur in a vacuum. And J.D. is joining us. He's with the Cleveland Clinic and and back in the nineties when I was developing a test very similar to this, I was very blessed to work with people at the Cleveland Clinic.

So can you give us a little more insight in terms of how not only USC, but how other academic institutions and hospitals work together to collaborate on cancer, all kinds of cancer diagnostics and therapeutics?

Peter Kuhn: Yeah. So I'm going to there's also another question around what are the tests being developed? So there is there's in many ways for early diagnosis, there is sort of two, I'm going to say schools of thought, but they come together. One is about bespoke, high precision, high accuracy, single cancer detection tests like what we are doing with the pink test for breast cancer, what, for example, Cologuard is trying to do for colon cancer.
 
At the same time, there are other groups that are building what's called multi cancer detection tests. Those two will go hand in hand. There is advantages and disadvantages. And and we can again spend some time talking about that as well. But fundamentally, we believe that the single cancer tests can perform so much better because we can actually exploit the biology of a particular cancer, as well as the anatomy of a particular organ where that cancer emerges.
 
 

Now, at the same time, back to Katie's question, the Cleveland Clinic, in fact, this organization that we built, which was which is called the Blood profiling, addressing cancer, blood Pact, brings together by now 50 groups from around the country. Everybody is a competitor with one another. Most of them are actually commercial competitors. When you see them publicly, they would they would they would butt heads like there is no tomorrow.
 
 However, we put this public private partnership together, what we call a pretty competitive partnership together. We're actually those very same people are sitting around the table on a daily basis because there is common problems that we need to solve ofhow we verify and validate how we built clinical trials and how we speed up the overall process of making these tests useful.
 
 So again, that's where this collaboration account around the country and really around the world is absolutely vital as we are making progress scientifically with that goal of really impacting all individual patients.
 
 

Amy Ross: Mm hmm. Very, very important points. We have a question by I believe was a student in your lab and is like would like to know, okay, beyond screening, how does the test we're talking about today perform and predicting recurrence or most importantly, response to therapy.

Peter Kuhn: So if I would have been able to convince you to go to grad school instead of med school, while I'm excited for all future patients of yours who will get that benefit, having you as a physician, you would probably be with both feet in the middle of test right now. And and so there is really just there's this observation that the cells and the anchor cells, the way they occur in individual patients or in and across groups of patients changes over time as the disease progresses.

So what we now have is we have our control. So women without breast cancer, we have early stage breast cancer. We also have what we call the first recurrence. So those are women who had just been diagnosed by an imaging study, just been diagnosed with the cancer, having come back. And we have late stage patients. What we don't have yet, which is a trial that we will be kicking off in the next couple of weeks, is to start enrolling patients in that watchful waiting period.

Now, that's a complicated experiment because it's going to take a very long time because, of course, we're not only interested in three year and five year survival in breast cancer. Luckily We have gone far beyond that. But we are interested in ten and 15 and 20 and 25 and 30 year survival, 35 year survival. So what is my individual residual risk after ten years after cancer, if that breast cancer coming back?

And how do I measure that? So that is that goal of that next set of studies given given how the specific time points are lining up? Sophia, I am absolutely convinced that we can fill in the blanks in between. But again, that's what these next trials need to need to start working out.

Amy Ross: Right. And I think that presents one of the complexities of cancer research. Yes, certainly detection is important. But then again, the endgame is how do we affect clinical benefit from this? How do we see what type of therapeutic can work so it doesn't just end? We're saying, yes, we know this, this patient has an occult cancer that's not being picked up by mammography.
 
 

This patient is, you know, likely going to have sites of metastatic disease. But how can we actually affect true clinical benefit? So that's why it takes all of us don't go slamming the M.D., is there, Peter, because it takes a village more than a village on all of this to get that going. So here's a really interesting question for John, too, because it from John, we've talked about certain markers of these cells and why it might be important to have them.
 
 So he has a very specific question about what we call the so-called triple negative breast cancer. So so for the difficulties and benefits of this blood test regarding triple negative breast cancer. So his specific question is, does the fact that Tnbc does not have a hormonal component present, that would be estrogen progesterone receptor there? Does it present special challenges for a blood test of this nature?
 
 And thus, is there any research specifically focused on triple negative with your approach?
 
 Peter Kuhn: Yeah. So incredibly important question, Of course, so triple negative in the average population only shows up in about 10 to 15, 15% of the diagnosis and so so with that, in our case control study, we didn't have enough triple negative patients to really make a definitive statement on this. John, we are working with two two groups, one in Chicago and winning Atlanta, where we will be recruiting patients in particular patients of African-American ethnicity and who are mutated to a much higher likelihood of actually be diagnosed with triple negative breast cancer.
 
So we will we do have late stage data sets that are triple negative specifically, which we are working up right now. So we know that they look different. What I can't tell you yet is this other question, is it more difficult or is it easier so that data will come through? I'm going to say over the next 18 months or so as we start enrolling patients and and in much more specific patient populations and start seeing the data coming through, we we are the current test.
 
 

The way we are approaching this is this test is not specific told them when receptor or her two receptor. So with that we build the test framework that can in fact see the full spectrum of breast cancer.
 
 Amy Ross: And I know in talking about this, I'm certain that we probably do have people in the webinar today who may be in that watchful waiting period. So if you're at home and you've been through your front line treatment and you've got a physician who's monitoring you, is there any way what is the best advice, Peter, that you can give somebody in that situation to try to enroll or be involved with some of these clinical trials?

Peter Kuhn: Yeah. So again, it is really important to recognize that, you know, A, there has never been a better time than today of being in that face. The number of treatment options that exist today is pretty amazing. You know, at the same time, of course, I'm going to say the same thing tomorrow and the day after and the day after and the day after.
 
As we're making scientific progress in this space, the most important thing is really having a and having a clinical partner in this and really being thoughtful around that clinical advice. Because what Jeff wrote today is still research use only. So it's really critical that our standard of care in breast cancer care is is really is really quite good.
 
In fact, it's pretty outstanding. And we we need to be really thankful of where we are with all of that. Having said that, I would always encourage everybody with your oncologist, with your provider, to always ask, where is it that you can participate in what is typically called observational studies? Does this the type of work that we do right where we say, Hey, we would like to recruit patients who want to participate in giving us a blood draw and giving us access to their breast cancer clinical data so that we can start building these correlations.
 
 

So there are and of course, ideally everybody would enroll with us. That would be our ultimate goal. But there are competing groups with us that might be much closer to where you live. By all means, enroll, please enroll, participate, because with that you will in fact participate in your own future. And that is just the most powerful thing that any one of us can actually do.
 
 

Amy Ross: And not only in our own futures, but future generations to come. When you look at where a cancer detection treatment now, it's so much more advanced. I know we would like much more progress, but again, cancer being so many different diseases where we stand now and with novel agents that are like thalidomide, the drug that was banned in the fifties from pregnant women is now a drug that has made a tremendous difference in patients with multiple myeloma.
 
So we have to recognize that with work of this sort, yes, we we want to be the ones to do it, to see benefit for not only ourselves and people of our generation, but how important this is going to be for generations to come to get there. So what I'd like to do here, Peter, we've had so many wonderful questions today and participation from the audience.
 
 

I really thank you. But what I'd like to do in our closing 5 minutes we have here, it was really an honor for you. And I remember you were sending me pictures from the White House when President Biden named you to the Cancer Moonshot. In closing, can you tell us a little bit more about your involvement and count with the Cancer Moonshot Project? And where do you think that has the ability to really be transformative with research in this country?
 
 Peter Kuhn: No, absolutely. So all of this really started in 2016, right? The the initiation of the cancer moonshot and the question of like, what is that? What does that even mean? What what is that? And what was really important was to do something quite simple, to stand up and set a goal. And the goal in 2016 was can we make ten years worth of progress in five years?
 
 
How many of us should be doing, which is like, Oh, just give us more money? But that wasn't the goal, right? It's actually it's a very different it's asking a very different question. Making ten worth of progress in five years. Now, when I look back at the time, if you would have asked me at the time will be have a an early breast cancer detection test in 2023 that we are ready to move forward, I would have said there is no way this is a far, far in the future vision.
 
 

But with the right students and the right mindset and the right support and infrastructure around us, we can in fact focus and we can in fact deliver on a goal like that. And I would actually say that we have far exceeded far, far exceeded our goal. You know, when when then when the when the launched Cancer Moonshot was we started again, the goal statement was really, really important here.
 
 And that was can we reduce cancer mortality by 50% now? I mean, whenever I come back to U.S., I typically bring questions back into class, into the classroom. And that brought that question and that goal setting of the Cancer Moonshot into the classroom. And one of the students, she raised her hand and she said, Professor Cohn, because, you know, I wanted to go on about how research needs to do this and that and the other.
 
 And she said, But Professor Cohn, 50%. Now, that's interesting because doesn't that mean that whatever we do has to reach every last person living in this country? And that I thought was actually profound, right? It wasn't about doing this niche thing with this one particular patient population. It wasn't about one individual scientific breakthrough. It was really about all of us together, meaning all of cancer research together, all of cancer care together, making sure that whatever we put forward is actually accessible to everybody living in this country.
 
 And so that to me, is the true power of having a common goal setting through the White House Cancer Moonshot that just brings people together, alliance, alliance people on a common goal and then starts allowing us to actually march forward.
 
 Amy Ross: Very important points there. We we made a considerable amount of progress, but there is a long way to go. So in closing, I would like to thank everybody who joined us today. We've had a wonderful team, Erica, Sarah and certainly our audio visual people who have done a remarkable job with this. So I want to thank not only Peter, all of his colleagues, not only Dornsife, the Michelson Center for Convergent Bioscience, but Dean Amber Miller.
 
I cannot say enough about her with the teams that she assembles with not only in research, but the entire depth and breadth of people at the Dornsife College. It really is remarkable. So but most importantly, it wouldn't be a webinar without our wonderful audience today. So thank you not only for your interest in the topic and thank you so much for your interest in what goes on at USC.
 
And as we always say, have a great day, but most importantly, Fight On!