Precision Medicine, AI & Metabolic Interventions for Advanced Cancer

•Cheap and scalable . For example, a patient questionnaire. The data is quite shallow, it has low predictive value, and is not very diagnostic.

•Expensive and manual . For example, MRI, CT, and PET scans. The data can be very diagnostic, useful, and sensitive, but you don't have a scanner in your house, and you can't be using it every week. Chris Gregg and his colleagues are aiming to fill the gap in the diagnostics marketplace by creating a tool (called Storyline) that is data rich, has high value and diagnostic and predictive capabilities, but is also very cheap and massively scalable. With Storyline, patients follow a clinical interview through a smartphone, then the interview and associated data are moved into the cloud, and it is analyzed using a variety of AI algorithms. They can pull out over 20,000 different microfeatures, such as facial movements, facial patterns, pallor, blinking rates, and speech analysis to get a deep understanding of what people are saying, what they're articulating, and how that compares to the thousands of patients that have been through the system before. It's not just what they say, but how they say it. Chris is also using Storyline to track his symptoms and hack his cancer, using the behavioral fingerprints of different types of pain. 3.Metabolic Treatment The next problem to solve to make cancer a chronic disease is to attack the mechanisms of resistance in the cancer cells. Building on the theory of adaptive therapy, how can you exploit or expand the cost of resistance to a treatment to make these treatments work more effectively, handicapping the resistant cells so that they can't take over? Nutrition (“food as medicine”) can attack metabolic pathways that resistant cells are using to be resistant to a treatment. There are many diets that are proven to work – such as inflammatory signals, glucose spikes, healing the microbiome, ketogenic, starving, and other diets. The primary problem to solve is compliance. Especially if you're sick, or you don't have a lot of social support, it's very hard to comply with a diet that would actually cause a meaningful clinical effect. Diet programs need to have palatable food, be easy to follow, and effective. Call to Action Chris is an amazing scientist and biohacker who is solving his cancer care. There are many kindred citizen scientists in our community, such as Jeff Krolick, who described his approach to supplements, including mushrooms, in this session. You can engage with Chris by joining his free “Uncharted Health” masterclass (at www.unchartedhealth.org). It will teach you the basic principles of cancer care and give you access to the Storyline symptom trackers, a nutrition program, and his “Metabolic Switching” ebook. You can email him at chris@storylinehealth.com . By donating your health data (e.g., biomarkers, tumor burden, scan results) and monitoring your symptoms, you will understand your own symptoms more deeply and accurately and help train the models that can track very subtle microsymptoms and predict disease activity. And with the meal program, you will be able to test the food delivery and quality. The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its Interventions for Cancer Control" Meeting Notes The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health. Discussion Outline 1.Introductions (0:00) 2.Adaptive therapy. (3:11) 3.Better approaches for adaptive therapy for cancer. (7:47) 4.How to use the QR code. (13:48) 5.How to help build the algorithms. (20:33) 6.The ketogenic diet and prostate cancer. (26:32) 7.The ketogenic diet and androgen deprivation therapy. (31:00) 8.What supplements do you take to fight cancer? (36:10) 9.Integrating EMR data into the storyline. (43:34) 10.What’s involved in growing your own mushrooms? (52:14) SUMMARY KEYWORDS patients, psilocybin, symptoms, cells, nk cell, storyline, diet, cancer, mushrooms, problem, treatment, idea, androgen deprivation therapy, moffitt cancer center, moffitt, data, test, metabolic, sensitive SPEAKERS Chris Gregg (48%), Jeff Krolick (30%), Brian McCloskey (13%), Russ Hollyer (6%), Rick Stanton (2%) Brian McCloskey We are very honored today to have Chris Gregg with us. Chris is a scientist working in neurogenetics and behavioral artificial intelligence to make precision medicine available to everyone. He's currently a tenured associate professor in the Department of Neurobiology and Anatomy and Human Genetics at the University of Utah School of Medicine, and he is the co- founder and CFO of Storyline Health. Chris is also a stage four cancer patient. He has a rare form of male breast cancer with estrogen receptor and progesterone receptor plus HER2. He has known for three and a half years that his life expectancy was three years. Four years ago he put together a program on extinction strategy using control of metabolic pathways, inflammatory signals, glucose spikes, etc., in a way to starve the cancer. He also leads a masterclass called Uncharted Health, which pulls together knowledge that is available today to more effectively control progression based on ecological and evolutionary principles. I'm very curious to see where Chris is going to lead us today. I see some synergy with some sessions that we've had with Bob Gatenby out of the Moffitt Cancer Center, who is an evolutionary biologist, and also runs their radiation oncology department. Chris Gregg 3:11 I've been looking forward to this talk for quite a while to be honest. One of the things that I hope to get out of it was an opportunity to share the projects that I've been trying to advance and to make some relationships with patients that I hope I could reach out to, to get advice, feedback, participation, etc., in some of the projects that I'm trying to get to move forward quickly. This picture is a nice picture of my family at Halloween. I had just been diagnosed and was going through chemotherapy, lost all my hair, but it was just perfect for a Dr. Evil costume. I have been battling away in the trenches with a stage four form of male breast cancer. As we all know, the standard of care leads you down a pathway that ultimately ends with the oncologist running out of drugs and everybody developing resistance to the treatments that are working effectively. I've been very intrigued and stood in this problem that Bob Gatenby and his group at Moffitt have been working on to turn advanced cancer into a manageable chronic disease , and doing my best to participate and contribute to that effort. For those of you who are not familiar with this approach and the concepts behind it, I just want to introduce it quickly. The idea is that any tumor is a mix of cells, some cells are sensitive to the treatment that you're taking at the time, for example, are sensitive to hormone signaling that you might block with your targeted therapy. And then you've got a subpopulation of cells that are partially resistant to the treatment sitting in there. And they're in part relying on hormone signaling and alternative signals. And then you've got cells that are fully resistant and potentially fully relying on alternative signals and not responding to hormone signaling or have found ways to get around the drugs. The central idea behind adaptive therapy, which is Bob's idea, is that this resistance comes at a cost. I'm very interested in the idea that you can exploit or expand that cost to make these treatments work more effectively. The way this works is you've got your tumor that's predominantly representing the sensitive population of cells, you go on your drug treatment, it attacks those cells. The idea is to never overtreat so that you lose the sensitive cells, you always want to keep, like a good gardener, a good population of sensitive cells, because you have control over them. And they in turn, have control over the resistant population through competition. And then you go on your holiday that allows the sensitive cells and the disease to essentially return to a defined level, and then go back on the drug treatment and knock it down, and then it comes back. You're a gardener, keeping those sensitive cells always available. So you're always responsive to your drug, and the disease becomes a chronic illness instead of a terminal illness. This approach shows promise in mouse models and in a small trial of prostate cancer. But the problem is that the vast majority of patients ultimately do progress, so that the resistant population takes over, and the treatment strategy fails. We're interested in coming up with improved approaches for adaptive therapy. I refer to the project that I've been working on as resistance-targeted adaptive cancer therapy to improve this, and essentially handicap the resistant cells so that they can't take over. There are a number of problems to solve to make this a reality for a lot of patients. We need to improve approaches for patient and disease activity monitoring. It's wonderful if you have a tumor marker that you can monitor, but many patients do not. And even if you do have a tumor marker that you can monitor, you need to be monitoring it so frequently that you will be tied to your hospital. If you live right next to your hospital, great. If you don't, then you've got a really big commute. It can be a real problem if you're going to live for 20, 30, or 40 years. We need solutions for monitoring that are scalable and easy to access. And we need integrative treatment solutions that can help prevent resistance by attacking this metabolic cost. All of this needs to be easy and deployable at scale. This is a little call for help. Shortly after I was diagnosed, I founded a company called Storyline which aims to use AI technologies to enable massively scalable precision medicine. There are a number of different solutions out there for monitoring patients’ health. They fall into three classes:

•They're very cheap, and very scalable, like a form or a questionnaire. But the data is quite shallow, it has low predictive value, and is not very diagnostic.

•There are fantastic technologies like MRIs, and CT, PET scans, etc. That can be very diagnostic and useful and sensitive, but they're expensive and manual. You don't have one in your house. You can't be using it every week.

•We were aiming to fill what we saw as a gap to create a technology that was data rich