Do individuals become refractory to a specific drug or an entire class of drugs? Do individuals when they become refractory to a treatment, is it to that particular drug or is it more like a class effect, that entire class of drugs? Actually, the answer is both. If you have an inhibitor which is potentially not very potent, in the space of FLT-3 inhibitors, we have seen some of this with, say, myelostorin, which is perceived to be a relatively weaker inhibitor. Now, some of the patients who relapse after being treated with myelostorin can still potentially respond to a more potent inhibitor if it is, you know, guillotinib for that matter, which is already approved and available. So that is one scenario. The other scenario is, say, a patient is being treated with a particular inhibitor targeting a particular mutation. Now, within that mutation, certain resistances can develop, right? Say for that matter, FLT-3 is again a great example. So FLT-3 has two kinds of mutations. It's an internal tandem duplication mutation or the ITD mutation or a point mutation. Now, some of the drugs, say, quizirtinib, which is in development, or sorafinib, which is not a drug approved for AML, but it's commercially available and it hits the FLT-3 ITD mutation. So those drugs, the patient is exposed to now, you can acquire a second mutation, which is the point mutation. And if you acquire a point mutation, you may be refractory to quizirtinib or sorafinib, but you may still be responsive to guillotinib. It's the same mutation in the same class of mutations, but at different sites in the same gene. So that's where, you know, you can be still responsive to another inhibitor in the same class. But then we see situations where you can acquire completely different mutation and become resistant to the entire class of mutation, entire class of drugs that are targeting that particular mutation. So now we have to talk about combining two different pathways, inhibitors, to actually address that resistance.
HealthTree • February 24, 2023