HAPPY NEW YEAR! (now for a little biology)

Patches tries to smother Linda in loose fur.

 



Okay, enough pussy-footing around.  We need to tackle PARP Inhibitors head on, wrestle them to the earth, and stomp on them.  What, you don’t have any idea what a PARP Inhibitor is, and furthermore you don’t give a damn?  Shame on you, and who cares about you, anyway?  I’m mainly writing this thing in the fervent hope that “PARP Inhibitor”, which I have looked up at least a dozen times, finally will stick in my head.”

First, definitions:  PARP code for “poly ADP ribose polymerase”.  Does that help?  Of course not.  “poly   you understand.  Polymerase is something that causes rapid duplication of a biochemical thing to occur. The term "ribose" refers to the structure of the molecule and is of no earthly significance here.  It turns out that ADP stands for adenosine diphosphate.   ADP is essential in the transfer of energy within cells, and so PARP refers to the mass production of something that is essential to life.  Add “Inhibitor” and you are referring to something that Inhibits life.  Now, why in heaven’s name would you want to do that?

Well, cancer cells are “life”, so we should inhibit the hell out of them.   The problem, of course, is to target cancer cells without shutting down all the rest of the organism at the same time.  Part of the answer lies in the fact that cancer cells divide and multiply much faster than normal cells, and thus toss up more potentially fatal DNA-replication errors to “inhibit”.  Also, many kinds of cancers have defective “repair” proteins, such as the well-known BRCA1 and 2 that are so important in ovarian and breast cancer, hence can’t fix the damage, whereas normal cells with normal BRCA can.  Ah, but something is missing so far.  The protein PARP1 fixes single-strand breaks in DNA, and if these breaks are not repaired double-stranded errors can ensue WHICH, in the absence of functional repair proteins, will cause the cell to croak.      

It appears that the complete activity of PARP proteins is not fully understood.  Many trials are underway.  Several drugs already have been tested – and failed.  Clovis Oncology has three PARP Inhibitor drugs in clinical trial right now, and other drug companies are in the hunt.  Can we allow ourselves to be optimistic?    Well, maybe.