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Navigating the Expanding Role of Precision Medicine
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Released: May 21, 2026

John Marshall
John Marshall, MD
Catch Up On All Episodes of Oncology Unscripted

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Ep 30 Main Topic: Navigating the Expanding Role of Precision Medicine

John Marshall, MD: John Marshall, Oncology Unscripted. Yeah. Episode 30. If you’ve watched all 30, we’ll send you a special gold-plated section of the East Wing that was torn down on the road here in Washington, DC. You’ll want that for your office, or maybe a doorstop or something. All 30, and you get a brick from the East Wing.

I’m, of course, lying. We don’t have that to give you.

We are going to focus, for the next really half year or more, around precision medicine. We’ll do our usual stuff, but we want to drill down on the impact of precision medicine in a variety of ways. You know, we went from having just a few tests: ER/PR. Triple-negative came later because that was a negative, if you will. BRAF comes along. There are some other markers here and there, fusions here and there. But let’s face it: we fronted all of this activity with companies that were willing to do the precision medicine, whether they got paid or not, in a way that collected data that demonstrated the benefit.

And over here, we had drug development going on because we had more and more knowledge about the different markers and the biology of cancer. So we were, in a sense, fronting our success through risk-taking, both by the precision medicine companies and the companies and all of us who are helping to make new therapies possible for our patients. And I think we can all look at each other and say that that was an investment that has paid off nicely, mostly in rich countries, mostly here in the United States. I’ve said before, I’ve been to events at ASCO where we just saw some new cool target and some new cool drug that had a good benefit rate for patients, and I’ll walk out with a friend from Europe or someplace else, and they’ll say, “Well, that’s great, but we are not going to be able to have that drug because of price.” And so, we need to disrupt this in a way so that we have more global access in order for precision medicine to make it to the next step.

But I really want to drill down on a few points that are really here, focused around the US and our own sort of local market.

And the first is: is precision medicine a choice, an option, or is it the standard of care? And we know in health care, we order tests mostly because it’s a hunch. We’re trying to make a diagnosis, this sort of thing. In some cases, we wouldn’t dare treat a patient without precision medicine.

I’m on service this week. We just admitted a lung cancer patient who, all we have is the tissue biopsy and a negative blood sample. So, the ctDNA on the blood is negative, but we still need to know. They might be hiding a fusion or something that’s not showing up in the blood. And so, even though we’re starting chemo because the patient’s sick, we have also gotten a biopsy and are sending that off for next-generation sequencing because there’s no way you’re going to treat a lung cancer patient without knowing the precision medicine results. In that case, we’ve known that to be true for breast cancer, for example. There’s no way you would treat a patient without knowing ER/PR, HER2, or triple-negative. Well, in colon cancer, we’ve talked about this before. Is it a requirement to do HER2 because only so few of them have it positive? What about RAS? Well, maybe soon. How about G12C? Not that common, but you’ve got a drug, right? About RAS mutations predicting resistance, you’ve got to know that, right? What about BRAF? It’s been a slow uptake on BRAF. MSI was pretty good.

So, I actually think precision medicine has shifted from a choice now being the standard of care. The reason that’s a risky thing to say is that if you haven’t done it, or if you haven’t interpreted it correctly for your patient, are you medically liable? Is that malpractice to not have acted on the mutation that exists or doesn’t exist in the patient in front of us? But I actually think that’s where we’re going, pretty much where we are for many cancers. And so, you need to make sure your practice is up to speed on all of this. I think most of us are, but there are still a bunch of times when it’s not being done or not done appropriately. So, we almost have to check on every patient to make sure it’s being done properly.

The second area I want to kind of drill down on is this idea around minimal residual disease, MRD, ctDNA testing, and precision medicine papers that are about to be presented in Chicago at ASCO. Many of them in the colorectal cancer space are this. Many of them are late-breaking abstracts, so I don’t know yet what they’re going to say, but usually late breaks are positive. Somebody knows the answer to what they’re going to say. But the other piece of this that’s really fairly striking is that a lot of these papers are done outside the United States. The research is being done outside the United States. And so, even though we’re getting access to these genetic tests, MRD testing, and stuff kind of free, it’s being paid for or covered by companies or by insurance one way or the other. So, we have access to it. In these other places where they don’t have access to it, that’s where they’re doing the research and generating this kind of data that I think will be practice-changing. So, do look out for the precision medicine, particularly around the MRD testing that we’re seeing increasingly out there in the literature, and yet another bunch of new papers coming up in Chicago in the colon cancer space, but also in other diseases as well. So, keep a nose out for that.

And then the last place I want to go is, you know, where I’m getting more and more questions about using blood testing to screen for cancer. There are only about five cancers we actually screen for officially. Screening is supposed to be cheap. It’s supposed to be noninvasive. It’s supposed to be easy. It’s for those patients who don’t have other risk. And so, you know, mammogram probably fits, Pap smears fit, but colonoscopies are not cheap and not noninvasive. We don’t screen for a bunch of bad cancers like pancreatic and gastric, and we start to screen for lung in the smokers now. But could it shift over to blood testing? And our patients love this idea. This is a very attractive idea to the consumer out there, to think that I’ve gone to my primary care doc, and they did a cancer-screening blood test, and it was negative. And I think that is good news. Let’s not kid ourselves. That is good news, and it’s where we’re going. But we’re going to be in this awkward window when a patient is completely reassured by that negative blood test and therefore is not going to get the normal screening. So, it’s going to take some time for us to demonstrate that that blood test is equal to or more effective than traditional screening that’s out there, and there will be a lot of pressure on us all to incorporate this. So, as you’re thinking about your ctDNA testing in patients with known cancer, think about that technology as it might inform a healthy person coming in in a primary care office and getting a blood test, kind of like a, you know, complete metabolic profile, but let’s throw in a cancer-screening test to see if there are any cancer genes floating around there. It’s where we’re going. I think it’s an important place to go, and I think the loop between treating MRD-positive and treating patients who are screen-positive may actually one day connect back itself. And I’m hoping that’s where all of this science goes. But we are going to work ourselves through this sort of awkward in-between time when we’re not quite so sure of what we’re doing. So, keep your nose up, keep a little bit of skepticism going forward. Embrace the new technology, but know what you know and know what you don’t know.

John Marshall for Oncology Unscripted.

This transcript has been developed using AI and edited for clarity.