Cancer Patient Lab Expert Webinar

“Liquid Biopsies”

Featuring: Peter Kuhn and Stephanie Shishido

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“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] Brian McCloskey and Brad Power August 24, 2022 “You need more than just one signal - a lot more.” Peter Kuhn “15 years ago, the model systems were mice and cell lines. With liquid biopsies, we have been able to start using humans as our model system.

” Peter Kuhn Meeting Summary Peter Kuhn, PhD, Dean’s Professor of Biological Sciences and Professor of Medicine, Biomedical Engineering, Aerospace & Mechanical Engineering, and Urology, University of Southern California; Founder and Chief Scientific Advisor, Epic Sciences; and Stephanie Shishido, PhD, Director of Clinical Research, CSI-Cancer, University of Southern California, led a discussion on the cutting edge of liquid biopsies and their ability to inform patients about their disease (“Do I have cancer?

”), predict progress (“How bad is the diagnosis?”), guide treatment decisions, (“Active surveillance vs. prostatectomy?”, “Will my treatment work?”), and monitor progress (“Is my treatment working?). Liquid biopsies hold out the promise of less invasive, lower cost, and more frequent capture of data about cancer and its environment, which could revolutionize treatment.

●How does liquid biopsy technology work? Liquid biopsies refer to collection of bodily fluids for analysis, usually blood draws, but can be of any fluid, including bone marrow aspirates.

The analysis can look for “circulating tumor cells” (CTCs), which are cancer cells that split away from the primary tumor and enter the circulatory system (metastasis); or “cell-free DNA”, fragments of DNA released into the bloodstream when cells die. The DNA signature of healthy cells is very different from cancer cells, called “circulating tumor DNA” (ctDNA).

●What can patients learn from a liquid biopsy, especially prostate cancer patients who are already getting blood draws to monitor their PSA biomarker? We tend to focus on the tumor cells, but there’s a lot of information in the environment around the tumor cells we can get from liquid biopsies that can help us understand the tumor and its dynamics.

For example, a blood test can tell if a patient has an androgen receptor variant (AR-V7), indicating that he will not respond to androgen-targeted therapies (such as abiraterone, enzalutamide, or apalutamide).

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] From UroToday, August 18, 2022, “Integration of Liquid Biopsies in Clinical Management of Metastatic Prostate Cancer - Beyond the Abstract”, Written by: Varsha Tulpule, Gareth J. Morrison, Mary Falcone, David I.

Quinn, Amir Goldkorn; Division of Medical Oncology, Department of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ●How close is the promise of this new technology to widespread access? This technology is in an early research phase that seems like “The Wild West”.

Peter Kuhn and Stephanie Shishido

Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] Brian McCloskey and Brad Power August 24, 2022 “You need more than just one signal - a lot more.” Peter Kuhn “15 years ago, the model systems were mice and cell lines. With liquid biopsies, we have been able to start using humans as our model system.

” Peter Kuhn Meeting Summary Peter Kuhn, PhD, Dean’s Professor of Biological Sciences and Professor of Medicine, Biomedical Engineering, Aerospace & Mechanical Engineering, and Urology, University of Southern California; Founder and Chief Scientific Advisor, Epic Sciences; and Stephanie Shishido, PhD, Director of Clinical Research, CSI-Cancer, University of Southern California, led a discussion on the cutting edge of liquid biopsies and their ability to inform patients about their disease (“Do I have cancer?

”), predict progress (“How bad is the diagnosis?”), guide treatment decisions, (“Active surveillance vs. prostatectomy?”, “Will my treatment work?”), and monitor progress (“Is my treatment working?). Liquid biopsies hold out the promise of less invasive, lower cost, and more frequent capture of data about cancer and its environment, which could revolutionize treatment.

●How does liquid biopsy technology work? Liquid biopsies refer to collection of bodily fluids for analysis, usually blood draws, but can be of any fluid, including bone marrow aspirates.

The analysis can look for “circulating tumor cells” (CTCs), which are cancer cells that split away from the primary tumor and enter the circulatory system (metastasis); or “cell-free DNA”, fragments of DNA released into the bloodstream when cells die. The DNA signature of healthy cells is very different from cancer cells, called “circulating tumor DNA” (ctDNA).

●What can patients learn from a liquid biopsy, especially prostate cancer patients who are already getting blood draws to monitor their PSA biomarker? We tend to focus on the tumor cells, but there’s a lot of information in the environment around the tumor cells we can get from liquid biopsies that can help us understand the tumor and its dynamics.

For example, a blood test can tell if a patient has an androgen receptor variant (AR-V7), indicating that he will not respond to androgen-targeted therapies (such as abiraterone, enzalutamide, or apalutamide).

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] From UroToday, August 18, 2022, “Integration of Liquid Biopsies in Clinical Management of Metastatic Prostate Cancer - Beyond the Abstract”, Written by: Varsha Tulpule, Gareth J. Morrison, Mary Falcone, David I.

Quinn, Amir Goldkorn; Division of Medical Oncology, Department of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ●How close is the promise of this new technology to widespread access? This technology is in an early research phase that seems like “The Wild West”.

ive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ●How close is the promise of this new technology to widespread access? This technology is in an early research phase that seems like “The Wild West”. We don't have clarity on which types of these liquid biopsies are relevant for which types of tumors at which stage in their progression.

It’s hard to find practitioners who are nimble and are willing to do serial liquid biopsies so we can be addressing genetic changes along the way. It's often hard to get these and other tests done, and they can be expensive. ●What's next? In prostate cancer and other cancers, like breast cancer, patients have lots of treatment choices.

We need to maximize the amount of information we can extract from liquid biopsies to make decisions that will yield better patient outcomes. Over the past three years there has been progress in analyzing liquid biopsies, from looking only at circulating tumor cells to understanding other cancer dynamics. There is research in combining multiple tests, e.g.

, cell-free DNA analysis, circulating tumor cells analysis, and single cell genomics analysis of the circulating tumor cells, enabling better targeting of cancer treatments. And new biomarkers are being researched in liquids which can predict disease progression and target cancer cells, such as a replacement for the PSMA PET test.

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.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] Meeting Notes SUMMARY KEYWORDS liquid biopsy, cancer, cell free dna, patient, cells, ctc, test, disease, super, blood, question, slides, imaging, wild west, androgen, waldo, rick, research, bit SPEAKERS Mike Yancey, Robert Ellis, Saed Sayad, John Laird, Jeff Waldron, Peter Kuhn, Rick Stanton.

Robert Ellis

I'm patient number five in the Prostate Cancer Lab. Our guests are Peter Kuhn and Stephanie Shishido. We're going to be talking about liquid biopsies, which I am very much interested in. Liquid biopsies enable less invasive, more frequent, and lower cost data about disease, which could revolutionize treatment.

We're going to be talking about the cutting edge of liquid biopsies in their ability to inform patients about their disease, predict progress and guide treatment decisions.

Peter Kuhn and Stephanie Shishido

artment of Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ●How close is the promise of this new technology to widespread access? This technology is in an early research phase that seems like “The Wild West”.

We don't have clarity on which types of these liquid biopsies are relevant for which types of tumors at which stage in their progression. It’s hard to find practitioners who are nimble and are willing to do serial liquid biopsies so we can be addressing genetic changes along the way. It's often hard to get these and other tests done, and they can be expensive. ●What's next?

In prostate cancer and other cancers, like breast cancer, patients have lots of treatment choices. We need to maximize the amount of information we can extract from liquid biopsies to make decisions that will yield better patient outcomes.

Over the past three years there has been progress in analyzing liquid biopsies, from looking only at circulating tumor cells to understanding other cancer dynamics. There is research in combining multiple tests, e.g., cell-free DNA analysis, circulating tumor cells analysis, and single cell genomics analysis of the circulating tumor cells, enabling better targeting of cancer treatments.

And new biomarkers are being researched in liquids which can predict disease progression and target cancer cells, such as a replacement for the PSMA PET test.

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.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] Meeting Notes SUMMARY KEYWORDS liquid biopsy, cancer, cell free dna, patient, cells, ctc, test, disease, super, blood, question, slides, imaging, wild west, androgen, waldo, rick, research, bit SPEAKERS Mike Yancey, Robert Ellis, Saed Sayad, John Laird, Jeff Waldron, Peter Kuhn, Rick Stanton.

Robert Ellis

I'm patient number five in the Prostate Cancer Lab. Our guests are Peter Kuhn and Stephanie Shishido. We're going to be talking about liquid biopsies, which I am very much interested in. Liquid biopsies enable less invasive, more frequent, and lower cost data about disease, which could revolutionize treatment.

We're going to be talking about the cutting edge of liquid biopsies in their ability to inform patients about their disease, predict progress and guide treatment decisions.

Liquid biopsies enable less invasive, more frequent, and lower cost data about disease, which could revolutionize treatment. We're going to be talking about the cutting edge of liquid biopsies in their ability to inform patients about their disease, predict progress and guide treatment decisions.

Peter Kuhn, PhD is founder and Chief Scientific Adviser at Epic Sciences, which develops liquid biopsies blood tests to inform cancer patients on their best course of therapy. Dr. Kuhn is the Dean's Professor of Biological Sciences, Professor of Medicine, Aerospace and Mechanical Engineering and Biomedical Engineering at the University of Southern California.

He also serves as the Director of the USC Michelson Convergent Science Institute in cancer and the Deputy Director of the Convergent Science Virtual Cancer Center. Dr.

Shishido is currently a postdoctoral researcher at the USC Michelson Center for Convergent Bioscience, focusing on the identification and characterization of circulating tumor cells from the liquid biopsy received from clinical trial cancer patients.

Her research interests focus on the interactions between the neoplastic cell and the microenvironment Epic's Comprehensive Cancer profiling approach uses multiple technologies to provide up to three types of analyses all based on a single blood draw.

Their proven and proprietary circulating tumor cell capabilities along with circulating tumor DNA and immune cell analysis allow for a clearer and more efficient picture for both prostate and breast cancer. Their approach reveals both genotypic and phenotypic data and can offer the most actionable personalized liquid biopsy available, which is specifically of interest to us.

The AR-V7 test identifies patients who are likely to be resistant to androgen-directed therapies such as abiraterone, enzalutamide, or apalutamide. The liquid biopsy test for AR-V7 is the first and only Medicare-reimbursed clinically validated predictive CTC liquid biopsy test for metastatic castrate-resistant prostate cancer.

Peter Kuhn

Stephanie has retired from her role as a postdoctoral fellow, and given the success of what she has done during that time is now Director of Clinical Research within CSI (Convergent Science Institute)-Cancer. She is responsible for a substantial portfolio of clinical research applications that range all the way into CAR-T therapies for prostate cancer.

We won't talk about this today. That is for a for a future conversation and why it is that we are involved with what we think are the best groups in the world working on this and how we think that we can hopefully help and support them in their mission to enable CAR-T therapy in prostate cancer, which has been one of the challenges up until now.

Today is really meant as a discussion and to provide information.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] I want to be most helpful to you guys.

could revolutionize treatment. We're going to be talking about the cutting edge of liquid biopsies in their ability to inform patients about their disease, predict progress and guide treatment decisions. Peter Kuhn, PhD is founder and Chief Scientific Adviser at Epic Sciences, which develops liquid biopsies blood tests to inform cancer patients on their best course of therapy. Dr.

Kuhn is the Dean's Professor of Biological Sciences, Professor of Medicine, Aerospace and Mechanical Engineering and Biomedical Engineering at the University of Southern California. He also serves as the Director of the USC Michelson Convergent Science Institute in cancer and the Deputy Director of the Convergent Science Virtual Cancer Center. Dr.

Shishido is currently a postdoctoral researcher at the USC Michelson Center for Convergent Bioscience, focusing on the identification and characterization of circulating tumor cells from the liquid biopsy received from clinical trial cancer patients.

Her research interests focus on the interactions between the neoplastic cell and the microenvironment Epic's Comprehensive Cancer profiling approach uses multiple technologies to provide up to three types of analyses all based on a single blood draw.

Their proven and proprietary circulating tumor cell capabilities along with circulating tumor DNA and immune cell analysis allow for a clearer and more efficient picture for both prostate and breast cancer. Their approach reveals both genotypic and phenotypic data and can offer the most actionable personalized liquid biopsy available, which is specifically of interest to us.

The AR-V7 test identifies patients who are likely to be resistant to androgen-directed therapies such as abiraterone, enzalutamide, or apalutamide. The liquid biopsy test for AR-V7 is the first and only Medicare-reimbursed clinically validated predictive CTC liquid biopsy test for metastatic castrate-resistant prostate cancer.

Peter Kuhn

Stephanie has retired from her role as a postdoctoral fellow, and given the success of what she has done during that time is now Director of Clinical Research within CSI (Convergent Science Institute)-Cancer. She is responsible for a substantial portfolio of clinical research applications that range all the way into CAR-T therapies for prostate cancer.

We won't talk about this today. That is for a for a future conversation and why it is that we are involved with what we think are the best groups in the world working on this and how we think that we can hopefully help and support them in their mission to enable CAR-T therapy in prostate cancer, which has been one of the challenges up until now.

Today is really meant as a discussion and to provide information.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] I want to be most helpful to you guys. I have slides because that's what an academic does. I have 30 slides that might be useful for this conversation, but I am just as happy,

Peter Kuhn and Stephanie Shishido

p and support them in their mission to enable CAR-T therapy in prostate cancer, which has been one of the challenges up until now. Today is really meant as a discussion and to provide information.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] I want to be most helpful to you guys. I have slides because that's what an academic does. I have 30 slides that might be useful for this conversation, but I am just as happy, if not even happier, if this is simply a conversation driven by questions that you have when you hear the key words "liquid biopsy.

" Let me start by asking, "What is it that comes to mind?" Rick Stanton 06:04 It was 2017. I was at Human Longevity. I heard about this company called Grail, and I thought, “This will never work”. It's like finding an attack submarine in deep water in the ocean, which is a job that I did. Then I was just amazed. I've told my wife who's just had breast cancer. She's under care at UCLA.

She had a lumpectomy, no genomic sequencing. I have been listening to “The Drive” podcast by Peter Attia, and his interview with Max Diehn from Stanford regarding circulating tumor cells. It came to me that my wife should have her primary tumor sequenced so that someday, circulating tumor cells will be able to identify reoccurrence before imaging.

I said, "You need to do this”, but it hasn't happened yet. I just had this conversation with her yesterday. I've been enthralled with Max Diehn's great podcast, and it's helping me understand the power of liquid biopsies. I'm under care at UCLA, and these things aren't even discussed. I'm also under the care of Dr.

T at Providence Saint Johns, and I'm hopeful that he will leverage new technologies like liquid biopsies and spatial phenotyping. Jeff Waldron 08:46 I've been working a little bit with a woman in France, Catherine Alix-Panabières. You may know her. One of the many interesting things is the distinction between ctDNA and CTCs, or cell-free DNA and ctRNA. I worked a little bit with Mass General.

I'm in the Boston area. We worked a little bit with Torpedo Diagnostics, which had a CTC launch that then got rolled back into Mass General, but not for original detection of cancer, but looking for remission or recurrence of cancer, particularly liver cancer, so they're using CTCs to do that.

It's interesting to see the way the applications are rolling out in some of these areas and to try to better understand the distinction between some of them. I'm not sure if that's in your scope for today. John Wadude Laird 10:05 I'm a medical doctor and medical advocate. I'm not a treating physician. My role is really to identify testing and treatment resources.

My questions are coming from that perspective. One, it seems like this is the Wild West. I don't have clarity on which types of these liquid biopsies are relevant for which types of tumors at which stage in their progression.

is really meant as a discussion and to provide information.

“Liquid Biopsies” (Peter Kuhn and Stephanie Shishido) [#23] I want to be most helpful to you guys. I have slides because that's what an academic does. I have 30 slides that might be useful for this conversation, but I am just as happy, if not even happier, if this is simply a conversation driven by questions that you have when you hear the key words "liquid biopsy.

" Let me start by asking, "What is it that comes to mind?" Rick Stanton 06:04 It was 2017. I was at Human Longevity. I heard about this company called Grail, and I thought, “This will never work”. It's like finding an attack submarine in deep water in the ocean, which is a job that I did. Then I was just amazed. I've told my wife who's just had breast cancer. She's under care at UCLA.

She had a lumpectomy, no genomic sequencing. I have been listening to “The Drive” podcast by Peter Attia, and his interview with Max Diehn from Stanford regarding circulating tumor cells. It came to me that my wife should have her primary tumor sequenced so that someday, circulating tumor cells will be able to identify reoccurrence before imaging.

I said, "You need to do this”, but it hasn't happened yet. I just had this conversation with her yesterday. I've been enthralled with Max Diehn's great podcast, and it's helping me understand the power of liquid biopsies. I'm under care at UCLA, and these things aren't even discussed. I'm also under the care of Dr.

T at Providence Saint Johns, and I'm hopeful that he will leverage new technologies like liquid biopsies and spatial phenotyping. Jeff Waldron 08:46 I've been working a little bit with a woman in France, Catherine Alix-Panabières. You may know her. One of the many interesting things is the distinction between ctDNA and CTCs, or cell-free DNA and ctRNA. I worked a little bit with Mass General.

I'm in the Boston area. We worked a little bit with Torpedo Diagnostics, which had a CTC launch that then got rolled back into Mass General, but not for original detection of cancer, but looking for remission or recurrence of cancer, particularly liver cancer, so they're using CTCs to do that.

It's interesting to see the way the applications are rolling out in some of these areas and to try to better understand the distinction between some of them. I'm not sure if that's in your scope for today. John Wadude Laird 10:05 I'm a medical doctor and medical advocate. I'm not a treating physician. My role is really to identify testing and treatment resources.

My questions are coming from that perspective. One, it seems like this is the Wild West. I don't have clarity on which types of these liquid biopsies are relevant for which types of tumors at which stage in their progression. The second concern I have is finding practitioners who are nimble and are willing to do serial liquid biopsy so we can be addressing genetic changes along the way.

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