PARP Inhibitors

PARP
Day 2 went very well in Houston
made it on time
in the meantime received positive news from El Paso
can apply for faculty time in clinic at University Medical Center
will be an honor if it gets through'
willing to cover at another Hospital over coming holidays to broaden my share of patients
while veterans physicians take it easy...will use any opportunity to shine.

Now Back to PARP inhibitor, (Poly ADP Ribose Polymerase), they are powerful drugs which follow our first law, they break DNA or cause failure to repair DNA mistakes.  Therefore cause automatic activation of intact P53 to induce automatic cell division Arrest. In other words, they act like Cisplatin and therefore will have a role in Ovarian cancer and by inference, will have a role in basal cell like Breast cancer (or triple negative Breast cancer).   Again, their limitation depend on preservation of P53 and all other molecules of that cascade.  They will also be limited by how fast the cell makes its repair.

Remember the 2nd law is the break of Microtubules/Microfilaments that leads to direct Caspase release, more powerful law.  This implies that a combination of PARP with Taxane (or Ixabepilone or Erubilin)will be the next non platinum combination of significance.

Following this logic, we predict an expanded role to Arsenic trioxyde. But fear of its use resides in its cardiac toxicity. But it acts like a Multikinase inhibitor because it interferes with so many cascades in the signal transduction.  Its limitation could also be that it may not lend itself to combination therapy because of "assumed" risk to the host.

Following-up on the 2nd Law discussed previously

Follow-up on the 2nd law discussed yesterday.
It is not by mistake that the 2 new drugs active in breast cancer, triple negative, target microtubules.
Indeed, both Erubilin and Ixabepilone target Microtubules.
I just took the test on Hope S. Rugo's presentation following the logic, passed the test without problem. So:
SHOULD WE USE CASPASE RELEASE IN LABORATORY AS PROOF OF CHEMOTHERAPY EFFECTIVENESS ON A STANDARD BASE (ROUTINELY), ON FRESHLY OBTAINED TISSUE, THAT IS!

Nature seems to tell us that when there is an error in the gene, we can repair this, but when the Microfilaments are destroyed, Mitosis is compromised and the cells' destiny is to die!  This is where the power of Vinorelbine comes from...Vinorelbine-Cisplatin is used as standard therapy for lung cancer, particularly in other parts of the world! 

DISCUSSION ON PARP INHIBITOR TO FOLLOW...