Re: [cml 2-, Tracey, Cheryl and Others Interested

[Guest guest]

Hi and All Others reading this,

As long as we are lreatively well, it's easy to forget that we even have CML and

the word CURE sits on a backburner while we go blithely along feeling somewhat

comfortable knowing that there are various treatment possibilities at this

point.

I recently began the dasatinib trial part 3 and am having a different

experience. I am feeling well and the side effects are minor compared to

Imatinib. However, I have to drive to Baltimore from Washington every two weeks

and sit for at least four hours while I go through a series of tests. This is

nothig compared to what some people are going through but it does force me to

think about CML more than I'd like and spend a lot more of time on healthcare

than I'd like.

Having been an adoptee I know what it's like to keep complaints to yourself

because, after all, you have it better than a lot of people. I will say that a

friend who's been through many different treatments for CML for many years is

finally responding to dasatinib and feels great. He says from what he knows of

other treatments in preparation that the word CURE will be a reality in not too

long a time. He's not a doc but knows a lot so maybe there are treatments that

will push CML over the edge into oblivion.

Cheers,

L

[ ] Gleevec inhibiting c-fms - Tracey and others

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.