[suzierose]

More Good News About Carfilzomib...enhances osteoblasts

by suzierose on Wed Apr 25, 2012 5:34 pm

One of the problems with the lytic bone disease that is a hallmark of multiple myeloma..is that even when the therapy successful kills the multiple myeloma cells...the holes in the bones are not filled in.

Now the new protesome inhibitors (PI) have been demonstrated to enhance the osteoblasts which are responsible for building bone, which means we can look forward to the lytic holes being filled.

"Carfilzomib [Kyprolis] and ONX 0912 effectively decreased multiple myeloma cell viability in vitro following continual or physiologic brief pulse treatment. These PIs were also able to overcome the growth advantage conferred by co-culture with human BM stromal cells or OCs. During their differentiation from mesenchymal stem cell precursors of mice and myeloma patients, physiologic concentrations of carfilzomib and ONX 0912 stimulated osteogenic differentiation and matrix mineralization and enhanced OB activity. In a similar manner, carfilzomib and ONX 0912 inhibited osteoclastogenesis from mouse and human progenitors and inhibited OC resorption. Importantly, the effects of these new PIs were exerted without being cytotoxic to OC/OB precursors. Daily oral administration of ONX 0912 to non-tumor bearing mice increased trabecular bone volume and enhanced bone formation. Finally, in a mouse model of disseminated human multiple myeloma, ONX 0912 decreased human RPMI-8226 tumor burden and prevented bone loss, with serum markers evidencing both bone anti-catabolic and anabolic effects.

Conclusion: In vitro and at physiologic concentrations and dosing, carfilzomib and ONX 0912 not only exert cytotoxic effects on myeloma cells, but also directly enhance OB formation and function and inhibit OC differentiation and resorption. In a disseminated human multiple myeloma mouse model, orally administered ONX 0912 showed anti-resorptive and bone-anabolic effects in addition to its anti-tumor properties. Our data demonstrate that carfilzomib and ONX 0912 exert combined beneficial effects of anti-myeloma activity and on associated-myeloma bone disease, with favorable pharmacologic and tolerability profiles being reported in patients."

https://ash.confex.com/ash/2011/webprogram/Paper39649.html

OC=osteoclast (chews bone)

OB= osteoblast (builds bone)

Onyx 0912 is new oral PI from Onyx