And no, for once, I won’t be asking expressly about whether or not the disease is curable! :)
The guest today is Dr. Rodger Tiedemann from Princess Margaret Hospital in Toronto. Dr. Tiedemann published papers last fall in which he discussed why Velcade and other proteasome inhibitors cannot cure Myeloma. The mechanism that they impact (the proteasome mechanism) doesn’t exist in the immature progenitor cells that cause Myeloma. He likened the use of these drugs to having a goat eat the weeds in your garden, but not getting rid of the roots.
This prompts a number of lines of inquiry — if it were me interviewing him, I’d get to all of the answers. I hope the format permits it!
– How does MM originate, and what is the lifecycle of a MM cell? What are the differences between a progenitor or precursor cell, and later MM cells? Do progenitor cells carry the chromosomal abnormalities, or does that happen as MM cells proliferate and develop more “genetic chaos”?
– If proteasome inhibitors do not work on the progenitor cells, what kids of therapies do? IMIDs (Revlimid, Pomalidomide, Thalidomide)? Alkalytors (Melphalan?) Anthracyclines (Adriamycin)? Or do we have nothing that works on them? Does this vary by disease biology (for example, del17 progenitor cells are more resistant to therapy than other kinds)? Where does immunotherapy enter into the mix?
– If we have something that works on them, could treating with multiple agents get both the progenitor and the more mature cells? If this isn’t the case, how does he explain people that appear to be cured?
We’ll see how much of this we get to — hopefully a lot, because it has a lot of ramifications (among them: if IMIDs don’t get the progenitors either, then we know definitively that the existing novel agents alone are not capable of curing anybody — this would put an end to one existing controversy and theory).
It should be an interesting conversation — hope some of you can join us!