RE:RE:RE:RE:RE:RE:RE:RE:RE:MTD and the FDAYes but we are still a few years away to see an ADC or a PDC using it being approved. It's on trial with many ADC, and that's in line with the fact that ADC needs more potent cytotoxic agents since they have a low loading rate, and also low tumor penetration and cell internalization. But if it works for ADC, it should be a killer in a good PDC system (peptide + target). On the PDC front, they are working on it with Dotatate, the peptide + linker of Lutathera, they only real PDC that is approved. They simply replace Lutetium 177 by Actinium 225. But since the kind of radiation is different and the toxicity much higher, they need to redo the whole development process.
juniper88 wrote: Jfm1330, I like your actinium-225 idea. It can probably overcome any resistance mechanisms as long as it goes in the cancer cell.
jfm1330 wrote: Resistance to docetaxel can come from multiple modifications in gene expression. The MDR efflux pump involving p-glycoprotein seems to be the main one, and the one Thera claim Th1902 allows to bypass, but there are other mechanism of resistance at the tubulin level, which is the target of docetaxel. Also, some inefficacy can be related to dose limitation, or, in other words, the impossiblity to achieve an intracellular concentration of docetaxel that is high enough. A wider therapeutic window linked with the concentrating effect of TH1902 should help to achieve much greater docetaxel concentrations of TH1902. So that and bypassing the MDR efflux pump should allow efficacy on many resistant cancer types, but there will be some cancers where docetaxel will just be ineffective, no matter how high the intracellular concentration.
AMoschitto wrote: On this point, with patients who may have developed resistance to taxol based on their previous treatment history... would bypassing the MDR pump still be effective in the way they talked about in the June presentation? I went to look back at that slide but they have
taken it out of the current presentation.
Curious if people here have thoughts about that as a potential disadvantage of this population (of course acknowledging more sortilin expression in late-stage cancers as making these patients ideal for TH1902 as well).