G’day Space Cadets
I have attached links to 3 review articles on the mechanisms of treatment resistance. They are technical and hard going (for me anyway). However there is a wealth of interesting stuff even among the few bits I think I understand. They discuss not only mechanisms, but how to disable them and resensitize treatment. There is discussion of some of the supplements familiar to readers, such as Indomethacin, Niclosamide, phytochemicals etc. The first 2, by Armstrong and Gao lists 8 kinds of mechanisms, testament to the adaptive complexity of our critter. Taken together, they are a pretty comprehensive review of what is known about resistance to Enz, Abi and the taxanes. There is a fair bit of crossover resistance, and it seems as if there are common mechanisms of resistance even when there are major differences in the mode of action of the drug. There is a glaring omission in the Armstrong and Gao discussions: high dose Testosterone (HDT, including BAT). The 3rd article by Mahommad et al is a review of what is known about testosterone treatments. I posted it once before but its worth bringing up again. They also identify 8 mechanisms of resistance that HDT could block. They are not quite the same as those identified by A&G but there is a fair bit of crossover. Interesting that HDT attacks over multiple mechanisms. We are dealing with a complex son of a bitch but it has a finite number of adaptive tricks.
Read the abstract, conclusion and the second last section (usually “future directions”) and decide if you want to dive in deeper.
ncbi.nlm.nih.gov/pmc/articl...
ncbi.nlm.nih.gov/pmc/articl...
mdpi.com/2072-6694/9/12/166
Second generation androgen receptor antagonists and challenges in prostate cancer treatment
Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells
ADT enhances the immune system
