Wednesday, November 28, 2012

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.



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