Gleevec inhibiting c-fms - Tracey and others

[Guest guest]

Hi all - this is a response to Tracey's from some time ago. First, thanks,

Tracey for discovering and posting this interesting abstract. I've spent a

bit of time looking up c-fms and trying to figure out what implications

there might be for its inhibition by IM. I can't say that I've reached any

useful conclusions beyond what the abstract suggests - that the effect could

turn out to be either beneficial or harmful, or both at once. Stimulation of

macrophages is critical to preventing and fighting off cancers (I spent a

lot of time last year looking into some fascinating research on this -

someday I'll write about it to this list), so you wouldn't want to inhibit

the production or activation of macrophages a great deal. On the other

hand, it appears that c-fms has a number of different roles in normal and

cancer cell physiology, and under some circumstances blocking its effects

could be a good thing.

Control of cellular process is so damnably complicated though. Many

stimulatory and inhibitory enzymes regulate every tiny activity in the cell,

and sometimes enzymes that stimulate a certain effect under one set of

circumstances will inhibit it when conditions change - so it's very hard to

predict what blocking any given molecule will do in an actual human even

once you have a pretty good sense of its actions in the test tube. This is

why we need clinical trials!

Bottom line, I guess, is that it's too early to say anything specific about

the IM/c-fms connection. It's a good reminder, though, that we're far from

knowing all there is to know about IM and its effects, and that it would be

great to find a cure for this disease, rather than just treat it year after

year with any drug, no matter how miraculous it may be.

Cheers,

R

From Tracey:

> I just found this abstract while surfing Pubmed. It seems that

> Gleevec not only inhibits bcr/abl, c-kit and PDGF (which we always

> knew), but now they've found that it also inhibits an enzyme called

> c-fms which plays a role in breast cancer, ovarian cancer and

> rheumatoid arthritis. Very interesting.

> Inhibition of c-fms by imatinib: expanding the spectrum of treatment.

>

> Dewar AL, Zannettino AC, TP, Lyons AB.

>

> Division of Haematology, Hanson Institute, Institute of Medical and

> Veterinary Science, Adelaide, South Australia.

> andrea.dewar@...

>

> We have recently demonstrated that imatinib also specifically targets the

> macrophage colony stimulating factor receptor, c-fms, at therapeutic

> concentrations. Although this finding has important implications with regard

> to potential side effects in patients currently receiving imatinib therapy,

> these results suggest that imatinib may also be useful in the treatment of

> diseases where c-fms is implicated. This includes breast and ovarian cancer

> and inflammatory conditions such as rheumatoid arthritis. We also speculate

> that imatinib may be used in diseases where bone destruction occurs due to

> excessive osteoclast activity, such as in the haematologic malignancy,

> multiple myeloma.