As our understanding of cancer biology continues to advance, this disease has come to be understood as many different diseases. As seen in the most recent
PARP clinical trial, mutations work with other proteins. Genes do not operate alone within the cell but in an intricate network of interactions.
The cell is a system, an integrated, intereacting network of genes, proteins and other cellular constituents that produce functions. One needs to analyze the systems’ response to drug treatments, not just one or a few targets (pathways).
In the functional profiling platform, where they can understand how
PARP inhibitors enhance the effects of drugs and drug combinations, the excellent results with
PARP inhibitors and BRAC mutants have been followed by striking response and survival data combining
PARP inhibitors with carbo-platinum and gemcitabine.
PARP inhibitors by inhibiting DNA damage response can enhance the effects of ionizing radiation, mustard alkylators, topoisomerase
inhibitors, platins, and intercalating agents. To date, they have observed good activity for the
PARP inhibitors as single agents in BRAC1 positive patients, and in some triple negative patients.
At Rational Therapeutics, Inc., in Long Beach, California, they’ve explored the biology of
PARP inhbitors in breast and other cancers. In these investigations, the lab applies the functional profiling platform to understand how
PARP inhibitors enhance the effects of drugs and drug combinations.
More interesting, will be the results combining the
PARP inhibitors with mustard alkylators, platins, and drug combinations to optimize
PARP inhibitor combinations.
This work is ongoing in triple negative and BRAC positive patients as well as other tumor types where the
PARP inhibitors may prove useful in the future. The
PARP inhibitors are turning out to be very useful, but you don't necessarily have to enter a clinical trial to fine that out.
http://www.rationaltherapeutics.com/
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