Episode 20: Cancer Genomics and Whole Person Care

We are a resource for learners, including every member of the live strong cancer institutes on track educational pipeline from middle school to residency, we are a growing collection of interviews, talks and experiences, the uncover, the myths and the uncertainties of cancer and careers in cancer in order to empower and inspire generations of thinkers and leaders.

This is cancer. An education and empowerment podcast by the live strong cancer institutes.

Welcome back. You’re back for another episode of cancer uncovered. I am Kristen Wynne senior program coordinator here at the live strong cancer institutes at the university of Texas at Austin Dell medical school. I am super excited to be here with you for our 20th full length episode. 24, a conversation on cancer, genomics, and whole person care before jumping in with Dr.

Jeannie Kowalski McGee. I want to flush out a few details. So Jeannie mentions the Texas health catalyst. The Texas health catalyst is a program at Dell medical school that provides researchers, innovators, and entrepreneurs, customized guidance on product development from industry and clinical experts.

Seed funding also mentioned is Gail’s calm model of whole person care. Gail is our department chair here at the LCI, Dr. Gail Eckhart, the calm model of whole person care refers to the way our LCI clinic at UT health. Austin is organized to provide specialized wraparound care for each individual patient.

You can learn more about the calm model of whole person care in episode one. Part of this model is making really specialized decisions about treatment for and with each patient. And part of that work includes Dr. Janie Kowalski McGee, Jeannie Kowalski McGee is a professor in the department of oncology at Dell medical school associate director of cancer, clinical genomics, and co-leader of the quantitative oncology program for the live strong cancer.

Thanks for having me, Kristin, my name is Jeannie qual ski McGee, and my particular work at Lynch. Joan. I think it’s really, really cool. It’s all quantitative and it integrates three quantitative areas for me. Cancer is quantitative, so cancer, biostatistics and bioinformatics. And my work at Lynch strong is to bring these three together.

To figure out what might be the best recommendation for treatment and therapies in cancer patients. That’s awesome. Could you break down for our audience? What you mean by quantitative? I get the question asked a lot. What exactly do you do here? So I look at results in tumor genomes. So let me, let me back up a bit, because I think I could help demystify some of the questions.

I get a lot. Uh, someone will say to me, oh, you do cancer genomes. Should I get tested for the BRCA one, two gene? And I’m like, well, everyone has the BRCA one, two gene as part of your genome. And so that is one of my favorite questions because it tells me that there’s. Some room for clarity and understanding about genes, your genome cancer, genomes, and tumor profiling.

So I really want to just kind of go back a bit and say, let’s talk genes. Okay. And then I’ll tell you awesome. What my quantitative contribution is and how I have the coolest job in the world. So Jean jeans are pieces of DNA. That code for something called a protein and there the instructions that run your body, keep your body in check.

Make sure everything’s kind of balanced and everything is working well. Now there’s about 30,000 genes that make up your genome and yes, the BRACA one, two gene. Everyone has BRCA one, two. Okay. That’s part of the 30,000. So what happens is you have cells that. The genes are inside yourselves and your cells have a genome and the cells divide, and sometimes there’s errors in the genome that happens.

And so one cell might not have an exact duplicate of another cell’s genome and these errors are called mutation. And what happens with cancer is that you might get some errors. Are these gene mutations, which are errors and they just kind of take off. So it’s like mistakes gone wild in. And that starts to become cancer cells.

So then you go from your normal cells to cancer cells. When those mutations or errors, just keep growing and growing, and then they have function. They have life, they start coming into play. Now this also happens with viruses as. Like with HIV, there was a viral genome, right? Corona virus, what are we sequencing viral genome.

Right. And so that’s what we’re looking for. Know, everything starts with your DNA, your genome. Again, we all have 30,000 genes. We all have the same genes, but we all have different processes and mistakes that happen. And some of those mistakes grow uncontrolled. And that’s how cancer your cancer genome comes around.

So then we do testing, right? So we do genetic testing. We do genomic testing, we do tumor profiling. What is the difference? They all involve testing those genes. Okay. They all involve gene testing, but they’re not done for the same reason. Uh, genetic test we’ll look at inherited mutations. So mutations that might have been affected by your mother or your father or sibling.

And that’s what the genetic testing will do. And it’ll look to see what is your risk of getting cancer, a particular cancer. And I believe our genetic counselor Khaleesi talked about this in a prior episode. So that’s more her domain and what she did. What I do is what’s called tumor profiling. Tumor profiling is what’s used to look at your cancer treatment.

It looks at a sample of your cancer cells for those unique errors or mutations that help the cancer to grow and spread. And your doctor will do a biopsy to remove some of the cells needed for this. And the test results help us to figure out what treatments are most likely to work best against targeting those errors in particular genes.

So my job is to really help look at that. Look at the tumor profiling and say, what are the errors that we’re looking at in the cancer cells that makes them specific to the cancer? And then let’s look at all the drunks that we have developed. And is there a drug that, you know, like an arrow is going to go and target, right?

Not cancer cell. That’s what makes molecular targeted therapy so specific, so personalized to, because every cancer cell is not going to be the same, their reproduction rate of the errors, and many things are going to be different for each. So that’s like a challenge. Every time I look at this result that we get from tumor profiling, it’s a challenge to say everyone’s different.

These things are connected differently. And you know, we have the same set of drugs, but everyone’s going to have a different arrow, you know, how do you, how do you get there? How do you target it? And in some people we don’t, we don’t have targets. And what do you do? What, what can we recommend for them? So I know that’s a long response, but I was really hoping to go through that particular part.

Um, because I think it’s important to differentiate the two different steps. No, that’s it. That’s really important. And I’m glad that you described that really thoroughly for us. So take it back to your statement about working quantitative leads. Put that puzzle piece back in there for us. Like how do we come full circle.

Cool. Thank you for reminding me. That was the initial question. So the quantitative part is I will take the results from the tumor profiling, all of those errors that I see, and I will look to find possibly different combinations of drugs. That might be helpful to not necessarily target maybe, but just has been shown to be helpful in patients with this particular BRCA one mutation that they respond to this drug more often than not quantitatively.

It means modeling. It means looking at associations that are out there in the big public databases and really mining the data for similar errors and other people’s cancer cells. And how did they respond to these drugs? So it’s bringing all of the modeling, the associations, you know, These very, I don’t want to use the terms, you know, but it’s bringing a lot of data mining into looking at what’s out there in public domain.

There’s so much data out there in the public domain. It’s using that as what’s called real-world evidence to show what can we bring to this particular patient? Right? What can we learn from what’s out there and bring it to the patient? And that takes quantitative methods, modeling and things. Does that help, right?

That helps a lot. Yes. So you’re looking at all the information that already exists about how people with this type of tumor or this type of error in their genes, how treatment worked for them maybe, or didn’t work for them and collecting all of that data to say, I think this would work for this person, with this cancer based on what we know from the data.

Exactly Kristin. That is exactly what I do in a nutshell. That is my job at let’s do from that’s awesome. I was going to say that is super cool. And I want to know, so you’re here doing this type of work at the live strong cancer institutes. How did you get to this place? How did you get to end up doing this work?

That that’s that’s great. And I like to add, you know, what motivates me to continue at 10. I actually started as an undergrad. Working with a transplant team. Um, and it was a famous transplant team. I actually worked with Dr. Thomas Starzl transplant team. Dr. Starzl was one of the first to do a human liver transplant and it was in Pittsburgh, Pennsylvania.

He had a whole team of people from clinical care. Right. And I was on the analysis side of that. And as an undergrad, I learned about survival analysis, how to determine the time to when the person would reject the Oregon. And that was very important. And so I saw that this was kind of cool. It was important from there.

I did a PhD thesis and Pittsburgh in modeling viral load in HIV patients. So HIV was. Epidemic at the time we were struggling with and viral load measured the amount of virus still in the patient. And how do we use that information to monitor whether any of the drugs were working? So it was a really cool opportunity from there.

I did a postdoc at Harvard and I, I just seem to be in the right place at the right time. So at Harvard, we just learned about sequencing the HIV. And I was one of the first to help design a clinical trial that looked at matching the HIV viral genome mutations or errors to. And so from there, I went to Hopkins with my first faculty position and I applied all this viral genome learning to now.

I was like, oh, cancers have genomes too. And we can do all this stuff in cancer now, too. And it’s kind of full circle. You know what? Corona virus, I have a lot of reminiscent about the HIV stagings and the research in there. So it’s interesting. I will say on a personal note, you know, what keeps me motivated is a personal connection with cancer.

My mom had breast cancer at a very early age, and I remember what she went through. You know, I witnessed that with her at the time. The only treatment course was

And as a result, the rest of her life, she had an effect from chemotherapy swallow, lymph nodes in her arm. And that just couldn’t be resolved. It was never resolved. So I saw the effects of that on her continence, on her ability to wear normal clothes on, on everything. Shortly when the pandemic started, one of my sisters was diagnosed with fresco.

And, you know, I saw firsthand virtually at least they had to change the course of her treatment. So what would have been normal standard of care for her particular diagnosis would have been her to get surgery first because it could be removed and taken out at the time. It was at the beginning of the pandemic and March.

And they didn’t have COVID protocols in place. No one knew what to do, how to do it. And so they said we can’t do this because it would involve no less than 25 people in and out of an or room. And we just, we can’t take the risks. So they had to change the course of their standard of care to instead give her chemotherapy first.

Um, now for that, her particular tumor. That was subjecting her to more than she would have probably needed it. And so it was very traumatic for her. She’s doing fine today. She’s doing well, thankfully, but, um, when it came time, when they had the protocols in place and then they went and did the surgery, they did the tumor profiling.

Cause they can take the cancer tissue out the tumor and the importance of that tumor profiling is because they want against standard. So they want it to know and make sure what treatment she might be likely to respond to. And so that’s an important after effect standard of care, but that that’s a key scene motivated.

Thank you for sharing that with us, that personal story and that it has affected your family and that that’s what keeps you motivated. I think. That’s beautiful. So we had heard about the molecular tumor board in a recent episode. Can you tell us more about what a molecular tumor board is and why it’s important and your lead role in that?

Thanks, Kristin, I appreciate that questions. I lead the live young molecular tumor board and it’s very important to many cancer centers. Many cancer centers will have a molecular tumor board of some sort in place. It’s a forum really for discussion and an oncologist will refer a particular patient to the molecular tumor board to discuss their tumor profile.

I remember we talked about what Taylor profiling is. My it’s the looking at the mistakes and the cancer cells of a patient to see, can we find a drug to shoot the arrow, right. Target that cancer cell. And that’s what we talk about. We talk about tumor profiling results. Well often get a result back and we will go through what the patient has been on, what worked, what didn’t work the tumor more often than not is not responding, which is why they have been referred to the molecular tumor board.

So it’s a form that’s open to all medical communities and education. Any student can attend it. A research fellow, the oncologist, nurse practitioners, anyone interested in it. The patient information is obviously de-identified for that reason. And you will see the discussion sometimes could lead to a whole expanded treatment recommendation.

Expand it from the particular report that we get. And my work in this molecular tumor. Has really gone off into again, computational and quantitative. What I try and do is take the tumor profiling results and gather up all the information that we can in public domain. And what information is helpful or not helpful in trying to get further insights on what might be going on with this patient.

Why are they not responding? Why is their tumor not responding to the treatment that they’re on? We come up with some hypothesis on that and equally important. What can we do? Is there a particular trial, can we identify a clinical trial locally or otherwise that the patient could then enter? And so that’s an important part of that.

The molecular tumor board discusses this. Come up with a summary of event and new this year, we’ve included as part of our molecular tumor board and, and investigation and inquiry like an education component. If someone wants to know about testing for RET gene mutations in lung cancer, what are they used for?

What kind of tests are out there? You know, we will take that kind of question. So we’re trying to keep all of us that lives. On our toes with what is current and what’s out there and that’s one way to do it because things change so fast in this field. It’s hard to keep on top of everything. Yeah, that’s fascinating.

I think on this podcast, we’ve touched on this as well at some point, but we have to wear boards, lots of tumor boards at LCI. But I think what’s interesting to highlight about this one is that you’re doing an immense amount of homework to find those answers, right? So like it’s not working, finding those clinical trials, making those recommendations, pulling the data.

And so, you know, the GI tumor boards were example run weekly, right? So they’re going through patients and they’re talking to one another and they’re coming up with a care plan. But if a patient is being presented, it, your tumor board, they’re sort of out of other options, right? Like the obvious things aren’t working.

So they’re saying genie, do the homework and see. What else may be out there for them at that point. That’s exactly what we do. We treat each patient as a, a mini research project, and that’s a good way to put it. That’s also why we right now are unable to take more than two cases a month. We, ours is monthly for that.

Because the right do we can’t really rely on, what’s been known because we’re really looking for what’s new. Right. And so the report will give us, what’s been known in the literature. What’s been known associations, but there’s so much new information to find where to find it, how to find it. What is about filtering out what is relevant?

What’s irrelevant. And. How to present it, what, what to present. And so it really is a lot of work, but it’s probably the most rewarding because I’m learning alongside with every case I’m learning more. And the more I learn, the more I can put into the next case and the next case. And so my lab on a necessity.

Has started to develop this platform, this computational platform that we’ve received, this Texas health catalyst award for. And that’s where that came from. We want to do more. We want to take more patients. We want to turn it around faster. And so one way to do that is can we automate any of these processes?

Right? That’s your first thing is, can you automate? And so that’s what we’re building. And we’re moving toward that so that we can respond quicker and help more patients. Right. Amazing. So tell us about w three, you sort of gave us the intro, but can you dive in and give us some more information about that project and how that’s going?

So w three stands for hold gene, hold data, whole profile for whole patient care. The idea behind W3C, the catalyst is the molecular tumor board. Right? And as I just said, we want to have more patients. That we can help and more frequently. And the way to do that was to automate what we do computationally W3C does that it automates the processes that we’re doing.

And so we will take a tumor profile report and we will extract from it key pieces that we use in our automated process and use that as. Into our platform with those key pieces, we then output many things. We output expanded treatment options. If they exist. We also look at profiles patterns. So we look to find patterns in the patient’s tumor.

Instead of looking at things separately, we look at things collected. When we start to do that, it’s like taking a magnifying glass and we’re able to zone in on parts of the patient tumor profile. No one has recorded before. And so that leads to a cool research area for many questions. So it’s hypothesis generating as well as helping in addition to the ultimately.

To help with patient treatments and clarifying that information, um, where we are with this platform now is we’ve applied for a proof of concept award internally that we’re waiting to hear from, and the Texas health catalyst we’re waiting to hear from them, whether we obtain funding for, um, a second half of this to build it out a little bit before.

I hope that we can scale it up and bill it out to cover the state of Texas. That’s incredible. That would be amazing. So dummy three is in production, so it’s not out necessarily in the world yet. This is something that’s been partially built, right? It’s in production to show that it can do what we say that it will do.

And so, you know, we’re at the testing phase. And we have also met with some companies to look at their investment in it as well. So in a perfect world, someday, when a company picks this up and has helped you produce. Platform, this web-based tool. What does that look like then for doctors and scientists?

Right? Is it something that they would log into on their laptop and we’d be able to put in some certain pieces of data and then get some information back, or what would that experience be like for them? That’s a great question, Kristen. My hope for its use is that it will be used. To have greater engagement in these molecular tumor boards.

We do such a big investigation and inquiry on the patient with what’s out there that I’m hoping it could be used to really create deeper engagement and insights through all of these different people on a tumor board, because with deeper engagement and insight, just like, you know, gal’s model of. You bring more pieces together and you connect more information, you know, more about the patient.

And what they’re experiencing. It can only lead to a more informed decision on their treatment. Thank you for sharing that with us. Um, and we’re excited to see how that comes together. Lastly, with the amount of time we have left, what words of wisdom do you have for our listeners? So we always ask our guests, you know, we, our audiences, future healthcare providers and health scientists, what words might you have for them?

The best that I could come up with is stay in the know to be a part of the know, be a part of the solution to these complex health problems. And you need to know information is power it’s knowledge to stay in doubt now. Yeah. Is there anything else Jeannie, that we didn’t cover or that I should have asked and did not.

If you asked me, do you. Like what you do, does your excitement there? I would say yes, because cancer is not cured, but we are going deep and we’re going deep with calm it’s cancer life. Re-imagined this is your cancer genome re-imagined. And so I think gals insight and new way, very early on to connect everything.

Is super critical. And you know, I’m hoping that this is a tagline behind it, right? Cancer genome re-imagine that’s what the insights do you look at things differently? You re-imagine.

Thank you so much, Dr. Kowalski McGee for taking the time to inform us and share with us the important work you are doing every day to improve treatment for cancer. If you have questions for us or an idea about a future episode, please email us@livestrongcancerinstitutesatdellmeddotutexas.edu. To find out more about the live strong cancer institutes, please visit Dell med dot U, texas.edu.

Please also follow our department chair, Dr. Gail Eckhart on Twitter. Gale at cart at cart is spelled E C K H a R D T. This is Kristin when with the lifts, strontium cancer institutes and cancer uncovered an education and empowerment podcast, challenging you to keep asking questions and to stay. Curious, thank you for listening and learning with us.

We’ll see you next month. .