Myc: FRIEND or FOE?

Linda w/Carolyn's wildcat, 2001

I got the idea for this post from the Fred Hutch e-newsletter, and specifically from an article entitled “Orphan drug used for sleep disorders may be potent cancer fighter.”  The article describes the work of Dr. Carla Grandori, who looks (from the appended photo) far too young to be heading her own lab.  However, she is, and it seems to be doing good work.  In a biochemical nutshell:  There is a gene, Myc  by name, that is implicated in several types of cancer, including something nasty called neuroblastoma, which kills children.  Unfortunately, a direct attack on Myc is infeasible, for two reasons.  First, it is difficult to attack with the kind of “stable, small molecule that would work as a cancer drug”, and second, Myc is needed for normal cell functions, so destroying it throughout the body would be a bad idea. 

However, there is a way out.  Myc genes in cancer divide and multiply very rapidly, thus furnishing an enhanced opportunity for mutation.  To keep the Myc gene in fighting trim, so to speak, proteins coded for by other genes, probably called DNA repair genes, must undo the damage.  This means that one can attack the repair genes, or (more accurately, I think) disable the proteins they code for – thereby limiting repair and disarming the Myc.  It so happens that there is a drug already on the shelf – its name is CSNK 1 epsilon – which does this admirably well.  Tests on mice indicate that it is a powerful weapon against (mouse) cancer.  Although they don’t look much like us (mice are cuter), apparently our small furry friend is very like us genetically, so maybe CSNK-1e will help us, too.  It is to be hoped.  Interestingly, CSNK1e was developed to combat sleep disorders.  It didn’t work.

And now, as I have nothing better to do, I’m going to toss out some random thoughts.

1)  I am more than a little confused about something.  If Myc is needed for normal cellular processes, how come it sometimes causes cancer?  My natural guess would be – because it mutates.  But if there are repair genes that code for stuff to repair cancerous Myc genes, how come they don’t fix the original mutation?  Or is there something much deeper that I overlook?

2) In an attempt an answer  the latter question, I tracked down, printed and attempted to read the original article by Dr. Grandori and her twelve (12!) co-authors.  It might as well have been written in Lithuanian!  The abstract is comprehensible, though, and there are some interesting illustrations. 

3) There appear to be members of the human genome that are classified as “undruggable”**.  This means, it seems, that they code for proteins that lack receptors to which “small-molecule therapeutic  agents” (apparently the stuff of drugs) can bind.  This from an article by Andrew Hopkins and Colin Groom, published in 2002.  There are about 30,000 genes in the human genome, and as many as a third  may be druggable.  Of course, you only want to drug the bad guys.

4)  Cancer research certainly relies heavily on fancy machines.  Dr. Grandori’s group investigated about 3,300 druggable genes, using a method called “high-throughput automated approach for testing of an arrayed siRNA library”.  siRNA means “small interfering RNA, and I know what most of the other words in that description mean – but I have no idea how her process works.    But, I’ll bet it’s expensive.  Maybe not as much as a battleship***, but surely as much as a light cruiser.  

**Another way to be “undruggable”, it seems, is to code for something absolutely essential.

*** This refers to posting “Musings”, from 6/13