An Integrative Platform of Whole Genome and Transcriptome Sequencing to Identify Additional Targets in Advanced Prostate Cancer - Jones Nauseef

March 22, 2023

Jones Nauseef joins Alicia Morgans to discuss a navigable interface for whole genome and transcriptome sequencing to identify additional targets in castration-resistant prostate cancer and neuroendocrine prostate cancer. This platform aims to help clinicians understand genetic information and how to incorporate it into their clinical decision-making for patients.


Jones T. Nauseef, MD, PhD, Weill Cornell Medicine, Division of Hematology & Medical Oncology; Sandra and Edward Meyer Cancer Center, New York, NY, USA

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi. I'm so excited to be speaking with Dr. Jones Nauseef, who's telling me a little bit about a recent publication, a poster at GU ASCO 2023, describing your experience with a platform that you and your team are producing, actually in combination with a company, to help clinicians understand genetic information and how they can integrate that information into their clinical decision-making for patients. Tell me a little bit about it.

Jones Nauseef: Absolutely. So we identified an unmet need that others have as well, which is as genetics, sequencing genomics, RNA-Seq, et cetera, all these wonderful technologies become cheaper and accessible, there still is a gap between the data that's produced and how to use that in an interpretable way that a clinician can make a clinical decision. So in a collaboration with Illumina, the New York Genome Center, and the company, Isabl, we took some of our data on prostate cancer ... So these are mainly patients with castration-resistant disease, but also both adeno and de novo neuroendocrine prostate cancer, and a handful of hormone-naive metastatic cases, and performed whole genome sequencing, whole transcriptome sequencing at the New York Genome Center and the Englander Institute for Precision Medicine, and use this data with the platform from a company to come up with a navigatable source that a clinician or researcher can look at, identify clinically actionable targets that may have not been apparent with a targeted sequencing or IHC, and make a decision for patients.

Alicia Morgans: That's great. So can you give me an example of when this might be used and how a clinician might engage with this type of a portal?

Jones Nauseef: I think it is important if when you see the poster to understand this is all retrospective in a pilot study that we've done and are planning to expand in the future to perhaps tumor-agnostic setting and a publication thereafter, and ultimately a tool that a clinician could use.

But as an example, we did identify some patients in this platform. And I want to comment on the platform as taking existing sequencing data, as I mentioned, whole genome, whole transcriptome data, and using both established tools and pipelines and some novel tools that the company is using, for example, to approximate high probabilities of homologous recombination deficiency, or HRD. And we did have examples of a patient that had metastatic CRPC, a rather aggressive disease, and on biopsy had anfrocrin characteristics. And the patient in real time was offered pembrolizumab, based on a high TMB. But looking retrospectively at the data from the platform, we're able to identify the patient had CDK12 type genomic instability, data that at the time may have prompted the choice of pembrolizumab earlier. And he actually had a complete response and remains in complete response till today.

Alicia Morgans: Wow. Well, that is great. And I think to your point, we often get this information, we may or may not always know how to integrate that both in our patients' clinical context, but then also how to think about different treatment options for that patient. So really pulling it together using plain language can be so helpful even for medical professionals, I would think, because one of the biggest barriers that I see to the use of genetic testing, whether it's germline or somatic, is that it's a little daunting if you haven't been doing this for a long time to understand, how do I use that information? If I run a test, I want to have an action on the other end. So this seems to be something that can be useful.

Jones Nauseef: Yeah, absolutely. And the opportunity to do this in the whole genome setting where portions of the genome that otherwise would not be queryable with exome or targeted sequencing as well as mutational signatures that can characterize genomic stability and other processes that may be clinically actionable in the future, is leveraging the power of whole genome sequencing.

Alicia Morgans: That's great. So you've already mentioned some next steps, but lay it out for us once more. Where do you go from here, since this abstract publication? How do we actually get this into our hands at some point?

Jones Nauseef: Yeah, so as I said, there's a gap here between those who understand the sequencing, can do the analysis, and those who are in the clinic with patients. And to bridge that gap is going to be an iterative process. And we're going back and forth with our colleagues on this pilot collaboration to try and refine their tools and hopefully make the transition from retrospective observation of what might have been useful or was useful, to making decisions for patients moving forward. For that to happen, of course the sequencing needs to be affordable, the turnaround time needs to be acceptable, and then what's highlighted in this poster, the data needs to be navigatable and interpretable for a clinician.

Alicia Morgans: Wonderful. Well, I look forward to the day when all of those things come together. We'll have you back to describe the portal. And hopefully we'll be unleashing it on clinicians everywhere so that they can use it to help their patients make the right decisions. I really appreciate your time and expertise.

Jones Nauseef: Thank you so much.