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Segment:1 Translational genomics.
[MUSIC PLAYING]
Segment:2 Why is translational genomics important in cancer research?.
BODOUR SALHIA: Translational research is so important for a number of reasons. First, it's bench to bedside. So it's making discoveries at the laboratory bench that are relevant and are going to be used for clinical care. And one of the reasons why translational research is so beneficial is because it allows us to get to clinical care in a much more direct way. Before the advent of modern technologies, which has essentially accelerated and enabled translational research, there were many more degrees of separation to get to that patient bedside and deliver optimal therapies and new therapies and better prognosticating markers and all of that.
BODOUR SALHIA: And so what we do with translational research is that we work with human samples. And together with the technologies that we have at our fingertips now, we really can accelerate the pace at which we get to that meaningful clinical care. And so, essentially, that's it, right? That's the most important thing is we want to improve human health.
BODOUR SALHIA: And we want to do it as quickly as possible and as accurately as possible. And that's what translational research allows us to do.
BODOUR SALHIA: [MUSIC PLAYING] So my lab has been working on cell free DNA methylation liquid biopsies for the last few years. And let me just explain why that's important and what that really means. So what we've known for several decades now is that there is circulating DNA in blood. And that's shed by the cells in your body, and, of course, also tumor cells.
BODOUR SALHIA: So tumor DNA gets shed into the circulation. That DNA that essentially circulates around in our blood or in patients with cancer harbor mutations and alterations that are associated with the tumor. And so essentially, what it allows us to do is with, again, modern technologies allows us to access that DNA from the plasma and assay it for mutations or methylation or copy number alterations. And it's, essentially, a non-invasive way to monitor cancer.
BODOUR SALHIA: And this is being used in my lab, now, for, really, the detection of minimal residual disease at the end of surgery for patients with breast cancer. And we're also applying this to other cancer types and to non-cancer indications because of the promise of the technology. And one of the real advantages of cell free DNA methylation, in particular, we believe is going to really revolve around the sensitivity and the specificity that that test has to offer.
BODOUR SALHIA: Essentially, when you're looking for minimal residual disease, you want to be doing better than what imaging can do. And so it's that disease that is-- you know, a patient might be told that they have no evidence of disease, but, in fact, they still harbor disease. It's just not detectable by current methods. And so a test like cell free DNA methylation, using a series of specific markers, will allow us to identify those cells that escape all current modalities right now. And that will help us predict and prognosticate patients' outcomes and put them on appropriate therapies to essentially eradicate recurrence. And that would be one of the main outcomes that we hope for in our test.
BODOUR SALHIA: Another area where cell free DNA methylation is becoming really hot is in the area of early detection for cancer. And the beautiful thing about DNA methylation that a mutation doesn't necessarily have the ability to do is it can bring you closer to the tissue of origin. So for example, if you want to be able to detect cancer several years before it actually becomes visible on a skin or becomes symptomatic in a patient, a single mutation, or even a series of mutation, may not help exactly pinpoint where that is. And the sensitivity to do that also may be harder to do with mutations. Although, even those technologies are improving drastically, where you can get to really, really low levels of detection.
BODOUR SALHIA: But with methylation, you have the ability to potentially pinpoint the organ that may have the cancer starting in it. And so that's where cell free DNA methylation has a lot of promise. And there's a lot of emerging technologies and efforts around really pushing this forward.
Segment:3 What are DNA methylation liquid biopsies?.
BODOUR SALHIA: [MUSIC PLAYING] So right now, for example, I'll just use breast cancer as an example. Determining whether women are at high risk of recurrence or at low risk of recurrence can be done at the time of diagnosis.
BODOUR SALHIA: However, those predictions are not always accurate. Furthermore, at the end of therapy, we don't know who's cured. And so we don't know if those women who are high risk, number one, were accurately classified as high risk. And if they were accurately classified as high risk, we don't know if they were cured. And the converse is true for the low-risk setting, as well, for people who were told that they are low risk. We don't know if they're cured. And so essentially, at the end of therapy, there's no more tissue, obviously, to go back and test to see how the methylation or the genetics have changed for that tumor.
BODOUR SALHIA: And so the only way to look at it is through circulating tumor DNA that may or may not be present. And so the idea is that we want to be able to, at the end of therapy, accurately tell somebody if they're actually still at high risk of recurrence. And that would be because there is still residual evidence of residual disease, evidenced by the fact that methylation-specific tumor methylation markers are still present in the body.
Segment:4 What other research focuses do you currently have? .
BODOUR SALHIA: [MUSIC PLAYING] In addition to cell free DNA methylation analysis, my lab is broadly interested in this idea of clinical epigenetics. So again, we're very interested in applying this technology to other cancers, in addition to breast cancer, and to non-cancer indications, as well. And we've got some efforts in the lab to do that.
BODOUR SALHIA: But we're also interested, globally, in cancer metastasis. And one area of specific interest to my lab is metastasis to the brain. And so my lab has been working also on developing, characterizing, and utilizing patient-derived xenografts from patients who had breast cancer or lung cancer metastasis. And we also have some other models from other metastases, as well-- from other primary sites, as well.
BODOUR SALHIA: And so brain metastasis is really a clinical dilemma. Those patients are often left out of clinical trials. The treatments really haven't improved or moved the needle very far at all in terms of survival and outcome. And it's not curable. Metastatic cancer, in general, is largely not curable, but in brain metastasis, it's really not curable.
BODOUR SALHIA: And while there is evidence of hope and case reports here and there and you hear of people who are living and living long with brain metastases, it's ultimately a fatal disease. And so what we lacked in the field were good models that represented the biology and the underlying genomic landscape of brain metastasis. My lab actually generated a bunch of brain metastasis PDX models that we characterized comprehensively.
BODOUR SALHIA: We know how well they do or don't represent the original tumor. And what we can do is then use that information that we know about the patient tumor, the information that we know was retained in the PDX tumor, and use that information to inform preclinical studies so that we can test new drug combinations and therapies in the mice, with the ultimate goal of informing clinical trials.
BODOUR SALHIA: There's a lack of clinical trials. There's just not enough of them for patients with brain metastases. And we want to change that by having real preclinical data that's relevant from human-derived samples to essentially say, you know, to the neurooncologist, we really should be looking at this combination.
Segment:5 What is the importance of engaging patients in translational research?.
BODOUR SALHIA: [MUSIC PLAYING] I truly believe that for patients who are so gracious and willing to donate their samples to research, that patients have the right to know about the outcomes of research.
BODOUR SALHIA: And the current state of translational research right now doesn't necessitate, mandate, or really even encourage that. And so essentially what happens is that we get all these de-identified samples that we try to obtain from our clinical partners. But those samples are de-identified, for the patient's protection, they're de-identified. And we don't know anything about those patients.
BODOUR SALHIA: We don't know what their stories are. They're just samples in a test tube. And I really wanted to change that for a number of reasons. I wanted to humanize research. I basically wanted to, number one, have more transparency in research and give the patients an opportunity to be informed about the sample that they gave. Granted, I'm not going to be able to tell patients and we shouldn't be-- during the research process-- how they should be treated or what their outcomes will be because it's still research, and that has to be made clear, but they should know what happened to their sample.
BODOUR SALHIA: If it led to something or if it didn't. And you know, humanizing research, to me, is becoming sort of a mission. And for that, I launched an initiative called The Bench With Bedside Initiative. And you can go to TheBenchWithBedsideInitiative.USC.edu to learn more about it. But it's all about engaging patients and collaborating with patients at the bedside.
BODOUR SALHIA: So translational research is bench to bedside so I say trans-relational research. So it's scientists at the laboratory bench collaborating with, engaging with patients at the bedside. And you know, we've had such a good response. And it's also allowed us to bypass the clinical infrastructure and go out into the community and actually recruit women to give blood directly.
BODOUR SALHIA: And we had a blood drive on October 6, 2018 at the Keck School of Medicine where we were able to recruit almost 60 women. And these women came to my lab to give blood. They got to see what the research lab looked like. Many of them got to see their blood being spun down right after they gave it. And it just provides-- it gives them hope. It makes them more invested.
BODOUR SALHIA: There is an interaction. There's a relationship that we're building with each other. And they understand where I'm coming from and I can understand better where they're coming from. And so where you have these two parallel roads that are generally walked right now, it's basically crossing those paths. And we-- because-- I think another thing that maybe patients and survivors and the public doesn't understand about scientists, sometimes, is that we're also humans.
BODOUR SALHIA: And we have all the issues that the humans have. And then, scientists need to be a bit more aware, especially even the lab folks, that this sample of blood that they're working with has a story behind it. It's a human life. And it just increases the urgency, it increases the accountability, it increases the transparency, and I think only good can come of that.
Segment:6 What are your AACR 2019 highlights?.
BODOUR SALHIA: [MUSIC PLAYING] The AACR is one of my favorite meetings that I attend to every year. And the reason is you get a real overview of the fields. You get to see all the new things that are happening and coming down the pipeline. You get to meet with people, new and old, that you know. I mean, you get to bump into friends and stuff like that. But really one of the things that I find is the highlight of the AACR is I feel that every year or so there is sort of a theme, a focus, a trend. And I just want to-- I'm always interested in knowing what that is.
BODOUR SALHIA: Of course, there are the areas of research that I am interested in. And so for example, this year, I want to be attending a lot of the talks on circulating tumor DNA. It's also interesting to see how little or how much is being done in your specific area of work. And so for example, there are several talks on circulating tumor DNA, but not much on cell free DNA methylation.
BODOUR SALHIA: And so it's just kind of good to see kind of what the landscape looks like and what the trends are. And so definitely-- like, for example, for circulating tumor DNA, we're beyond, we can do it, we can detect mutations in blood. It's all about sensitivity and specificity. So there are a lot of emerging technologies that are enabling that. And there are different challenges for different analytes, so whether it's cell free DNA or tissue DNA, and whether you're looking at methylation or mutations or different challenges.
BODOUR SALHIA: And so it's nice to see who's trying to overcome these challenges. And it just always gives you some new ideas to go back home with and sort of maybe rethink things a little bit. So I always try to follow what are the trends, and where are the areas that I maybe you should be getting more up to speed with. It's impossible to know everything about everything, obviously, and to keep up with everything.
BODOUR SALHIA: But it kind of gives you a direction sometimes, especially for the areas that you are not completely focused in. And you know, all the time, you kind of, oh, I never thought about-- I never thought-- it's not my area, but I never thought about that, you know? And so it's really good at sort of getting you to originate new ideas.
BODOUR SALHIA: [MUSIC PLAYING]
Segment:1 Translational genomics.
[MUSIC PLAYING]
Segment:2 Why is translational genomics important in cancer research?.
BODOUR SALHIA: Translational research is so important for a number of reasons. First, it's bench to bedside. So it's making discoveries at the laboratory bench that are relevant and are going to be used for clinical care. And one of the reasons why translational research is so beneficial is because it allows us to get to clinical care in a much more direct way. Before the advent of modern technologies, which has essentially accelerated and enabled translational research, there were many more degrees of separation to get to that patient bedside and deliver optimal therapies and new therapies and better prognosticating markers and all of that.
BODOUR SALHIA: And so what we do with translational research is that we work with human samples. And together with the technologies that we have at our fingertips now, we really can accelerate the pace at which we get to that meaningful clinical care. And so, essentially, that's it, right? That's the most important thing is we want to improve human health.
BODOUR SALHIA: And we want to do it as quickly as possible and as accurately as possible. And that's what translational research allows us to do.
BODOUR SALHIA: [MUSIC PLAYING] So my lab has been working on cell free DNA methylation liquid biopsies for the last few years. And let me just explain why that's important and what that really means. So what we've known for several decades now is that there is circulating DNA in blood. And that's shed by the cells in your body, and, of course, also tumor cells.
BODOUR SALHIA: So tumor DNA gets shed into the circulation. That DNA that essentially circulates around in our blood or in patients with cancer harbor mutations and alterations that are associated with the tumor. And so essentially, what it allows us to do is with, again, modern technologies allows us to access that DNA from the plasma and assay it for mutations or methylation or copy number alterations. And it's, essentially, a non-invasive way to monitor cancer.
BODOUR SALHIA: And this is being used in my lab, now, for, really, the detection of minimal residual disease at the end of surgery for patients with breast cancer. And we're also applying this to other cancer types and to non-cancer indications because of the promise of the technology. And one of the real advantages of cell free DNA methylation, in particular, we believe is going to really revolve around the sensitivity and the specificity that that test has to offer.
BODOUR SALHIA: Essentially, when you're looking for minimal residual disease, you want to be doing better than what imaging can do. And so it's that disease that is-- you know, a patient might be told that they have no evidence of disease, but, in fact, they still harbor disease. It's just not detectable by current methods. And so a test like cell free DNA methylation, using a series of specific markers, will allow us to identify those cells that escape all current modalities right now. And that will help us predict and prognosticate patients' outcomes and put them on appropriate therapies to essentially eradicate recurrence. And that would be one of the main outcomes that we hope for in our test.
BODOUR SALHIA: Another area where cell free DNA methylation is becoming really hot is in the area of early detection for cancer. And the beautiful thing about DNA methylation that a mutation doesn't necessarily have the ability to do is it can bring you closer to the tissue of origin. So for example, if you want to be able to detect cancer several years before it actually becomes visible on a skin or becomes symptomatic in a patient, a single mutation, or even a series of mutation, may not help exactly pinpoint where that is. And the sensitivity to do that also may be harder to do with mutations. Although, even those technologies are improving drastically, where you can get to really, really low levels of detection.
BODOUR SALHIA: But with methylation, you have the ability to potentially pinpoint the organ that may have the cancer starting in it. And so that's where cell free DNA methylation has a lot of promise. And there's a lot of emerging technologies and efforts around really pushing this forward.
Segment:3 What are DNA methylation liquid biopsies?.
BODOUR SALHIA: [MUSIC PLAYING] So right now, for example, I'll just use breast cancer as an example. Determining whether women are at high risk of recurrence or at low risk of recurrence can be done at the time of diagnosis.
BODOUR SALHIA: However, those predictions are not always accurate. Furthermore, at the end of therapy, we don't know who's cured. And so we don't know if those women who are high risk, number one, were accurately classified as high risk. And if they were accurately classified as high risk, we don't know if they were cured. And the converse is true for the low-risk setting, as well, for people who were told that they are low risk. We don't know if they're cured. And so essentially, at the end of therapy, there's no more tissue, obviously, to go back and test to see how the methylation or the genetics have changed for that tumor.
BODOUR SALHIA: And so the only way to look at it is through circulating tumor DNA that may or may not be present. And so the idea is that we want to be able to, at the end of therapy, accurately tell somebody if they're actually still at high risk of recurrence. And that would be because there is still residual evidence of residual disease, evidenced by the fact that methylation-specific tumor methylation markers are still present in the body.
Segment:4 What other research focuses do you currently have? .
BODOUR SALHIA: [MUSIC PLAYING] In addition to cell free DNA methylation analysis, my lab is broadly interested in this idea of clinical epigenetics. So again, we're very interested in applying this technology to other cancers, in addition to breast cancer, and to non-cancer indications, as well. And we've got some efforts in the lab to do that.
BODOUR SALHIA: But we're also interested, globally, in cancer metastasis. And one area of specific interest to my lab is metastasis to the brain. And so my lab has been working also on developing, characterizing, and utilizing patient-derived xenografts from patients who had breast cancer or lung cancer metastasis. And we also have some other models from other metastases, as well-- from other primary sites, as well.
BODOUR SALHIA: And so brain metastasis is really a clinical dilemma. Those patients are often left out of clinical trials. The treatments really haven't improved or moved the needle very far at all in terms of survival and outcome. And it's not curable. Metastatic cancer, in general, is largely not curable, but in brain metastasis, it's really not curable.
BODOUR SALHIA: And while there is evidence of hope and case reports here and there and you hear of people who are living and living long with brain metastases, it's ultimately a fatal disease. And so what we lacked in the field were good models that represented the biology and the underlying genomic landscape of brain metastasis. My lab actually generated a bunch of brain metastasis PDX models that we characterized comprehensively.
BODOUR SALHIA: We know how well they do or don't represent the original tumor. And what we can do is then use that information that we know about the patient tumor, the information that we know was retained in the PDX tumor, and use that information to inform preclinical studies so that we can test new drug combinations and therapies in the mice, with the ultimate goal of informing clinical trials.
BODOUR SALHIA: There's a lack of clinical trials. There's just not enough of them for patients with brain metastases. And we want to change that by having real preclinical data that's relevant from human-derived samples to essentially say, you know, to the neurooncologist, we really should be looking at this combination.
Segment:5 What is the importance of engaging patients in translational research?.
BODOUR SALHIA: [MUSIC PLAYING] I truly believe that for patients who are so gracious and willing to donate their samples to research, that patients have the right to know about the outcomes of research.
BODOUR SALHIA: And the current state of translational research right now doesn't necessitate, mandate, or really even encourage that. And so essentially what happens is that we get all these de-identified samples that we try to obtain from our clinical partners. But those samples are de-identified, for the patient's protection, they're de-identified. And we don't know anything about those patients.
BODOUR SALHIA: We don't know what their stories are. They're just samples in a test tube. And I really wanted to change that for a number of reasons. I wanted to humanize research. I basically wanted to, number one, have more transparency in research and give the patients an opportunity to be informed about the sample that they gave. Granted, I'm not going to be able to tell patients and we shouldn't be-- during the research process-- how they should be treated or what their outcomes will be because it's still research, and that has to be made clear, but they should know what happened to their sample.
BODOUR SALHIA: If it led to something or if it didn't. And you know, humanizing research, to me, is becoming sort of a mission. And for that, I launched an initiative called The Bench With Bedside Initiative. And you can go to TheBenchWithBedsideInitiative.USC.edu to learn more about it. But it's all about engaging patients and collaborating with patients at the bedside.
BODOUR SALHIA: So translational research is bench to bedside so I say trans-relational research. So it's scientists at the laboratory bench collaborating with, engaging with patients at the bedside. And you know, we've had such a good response. And it's also allowed us to bypass the clinical infrastructure and go out into the community and actually recruit women to give blood directly.
BODOUR SALHIA: And we had a blood drive on October 6, 2018 at the Keck School of Medicine where we were able to recruit almost 60 women. And these women came to my lab to give blood. They got to see what the research lab looked like. Many of them got to see their blood being spun down right after they gave it. And it just provides-- it gives them hope. It makes them more invested.
BODOUR SALHIA: There is an interaction. There's a relationship that we're building with each other. And they understand where I'm coming from and I can understand better where they're coming from. And so where you have these two parallel roads that are generally walked right now, it's basically crossing those paths. And we-- because-- I think another thing that maybe patients and survivors and the public doesn't understand about scientists, sometimes, is that we're also humans.
BODOUR SALHIA: And we have all the issues that the humans have. And then, scientists need to be a bit more aware, especially even the lab folks, that this sample of blood that they're working with has a story behind it. It's a human life. And it just increases the urgency, it increases the accountability, it increases the transparency, and I think only good can come of that.
Segment:6 What are your AACR 2019 highlights?.
BODOUR SALHIA: [MUSIC PLAYING] The AACR is one of my favorite meetings that I attend to every year. And the reason is you get a real overview of the fields. You get to see all the new things that are happening and coming down the pipeline. You get to meet with people, new and old, that you know. I mean, you get to bump into friends and stuff like that. But really one of the things that I find is the highlight of the AACR is I feel that every year or so there is sort of a theme, a focus, a trend. And I just want to-- I'm always interested in knowing what that is.
BODOUR SALHIA: Of course, there are the areas of research that I am interested in. And so for example, this year, I want to be attending a lot of the talks on circulating tumor DNA. It's also interesting to see how little or how much is being done in your specific area of work. And so for example, there are several talks on circulating tumor DNA, but not much on cell free DNA methylation.
BODOUR SALHIA: And so it's just kind of good to see kind of what the landscape looks like and what the trends are. And so definitely-- like, for example, for circulating tumor DNA, we're beyond, we can do it, we can detect mutations in blood. It's all about sensitivity and specificity. So there are a lot of emerging technologies that are enabling that. And there are different challenges for different analytes, so whether it's cell free DNA or tissue DNA, and whether you're looking at methylation or mutations or different challenges.
BODOUR SALHIA: And so it's nice to see who's trying to overcome these challenges. And it just always gives you some new ideas to go back home with and sort of maybe rethink things a little bit. So I always try to follow what are the trends, and where are the areas that I maybe you should be getting more up to speed with. It's impossible to know everything about everything, obviously, and to keep up with everything.
BODOUR SALHIA: But it kind of gives you a direction sometimes, especially for the areas that you are not completely focused in. And you know, all the time, you kind of, oh, I never thought about-- I never thought-- it's not my area, but I never thought about that, you know? And so it's really good at sort of getting you to originate new ideas.
BODOUR SALHIA: [MUSIC PLAYING]
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