A POTPOURRI OF POORLY UNDERSTOOD BIOLOGY

Spring us in the air!

PFS = Progression-free survival.  Means:  You’ve got it, it will probably get you in then end – but right now you are in remission and this stuff helps prolong it.  A lot better than nothing, certainly, but not what you really want, which is ….

OS = Overall survival.  A lengthened lifetime.  The Holy Grail here is something that prolongs OS indefinitely.  In other words: a cure.   The search still goes on.

PARP = Poly ( ADP-ribose) polymerase.  This is a protein that, among other things, repairs double-stranded breaks in cellular DNA.  Double-stranded breaks (and other imperfections) most commonly occur during cell division.  If a break is not repaired the cell will die.  Thus…

PARPi = PARP inhibitor.  This is a variety of drug that inhibits the activity of PARP.  As cancer cells divide much more frequently than normal cells, PARPi drugs are a weapon against cancer.  There are several already approved by the FDA: olaparib, rucaparib, niraparib, talazoparib.  As far as I can see, these are mainly (only?) useful for cases of OVCA and breast cancer where germ-line mutations of the genes BRCA1, BRCA2 and (something I had never heard of) PALB2 are involved.  Thus, these drugs are not universally useful and, moreover, have nasty side effects.  PARPi treatments are good for PFS, but how they affect OS is questionable. 

PARG = Poly (ADP-ribose) glycohydrolase.  And now we get, at last, to what spurred me to write this blog.  This stuff’s mission in life is to “catabolize” (i.e., get rid of) PARP.  Without it, PARP accumulates, and the cell dies.  So, inhibit PARG , PARP accumulates, and the (cancer) cell croaks.  At least, so reason scientists at U. Manchester, U.K.  The blurb cited below does not make it clear whether PARGi drugs can be useful in OVCA cases not involving BRCA, etc., mutations.  I can’t see why they SHOULD but, hell, as I have said many times before – what do I know?

https://www.eurekalert.org/pub_releases/2019-03/uom-nco031919.php