I think it’s going to be game-changing. I mean, we’re still in the very early stages, I think, of CSF as a liquid biopsy source, but I think the ability to detect these very specific kind of molecularly defined biomarkers like cell-free DNA variant alleles, D-2-hydroxyglutarate for patients with IDH mutant gliomas. And then even in plasma, I mean, when we’re looking at these amplified junctions, they’re often associated with EGFR, CDK4, and other things like that, which can be molecularly targeted...
I think it’s going to be game-changing. I mean, we’re still in the very early stages, I think, of CSF as a liquid biopsy source, but I think the ability to detect these very specific kind of molecularly defined biomarkers like cell-free DNA variant alleles, D-2-hydroxyglutarate for patients with IDH mutant gliomas. And then even in plasma, I mean, when we’re looking at these amplified junctions, they’re often associated with EGFR, CDK4, and other things like that, which can be molecularly targeted. I think one of the limitations that we’ve had in the field of neuro-oncology, again, has been our inability to access tissue longitudinally, unlike in other fields like breast cancer, where there’s a lower threshold to be able to biopsy and to be able to determine whether or not there is treatment response to a molecularly targeted agent. So I really see CSF and hopefully plasma being able to fit into a new paradigm where we have patients that come with a brain tumor, they undergo either a biopsy or a resection, we get that tissue and we have an idea of, you know, here’s the molecular profile, what sort of agents can we use to target these molecular alterations, you know, either with or without standard of care, depending on if they’re expected to be, you know, sensitive to those agents, and then putting them on that agent and then using that CSF or plasma before and after the agent to see whether or not there has been on-target effects. The other thing too, of course, when we’re thinking about precision medicine and these sort of molecularly targeted agents is the ability to look at treatment resistance. And so I think one of the things that we’ve been able to see is that if we target one mutation, there’s often a whole outgrowth of other mutations that can come, and we can see that in CSF. So I think that then lends itself really well to sort of response-adaptive trials where we’ll put a patient on a therapy that’s, you know, specifically ideal for them based on their molecular profile at the time. We can look at the CSF and see, all right, did it have its on-target impact? What’s the overall disease burden looking like? Is it going down? Is it going up? And are there new mutations that are emerging that can then be targeted? And I think with all of that information in hand, it’ll allow us to have more shots on goal for patients. Right now, our limitation in neuro-oncology has often been that we’ll put a patient on a therapy and then wait for outcome measures like overall survival and progression-free survival, which are, you know, necessary overall, but they’re really mechanistically impoverished and we need to have more biological information. And we have patients who are interested in also getting that information to help guide their treatment. So I think the liquid biopsy space is going to hopefully, I think, revolutionize the neuro-oncology pathway, especially for in the context of clinical trials and all this, like these cool new agents that we’re getting to see every single year. So it’s an exciting time to be in that space.
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