A bit on this new class of cancer drug, gathered from around the Internet & from talking to oncologists.
“Poly ADP-ribose polymerase, or PARP, plays a key role in DNA repair by detecting and initiating repair if a DNA strand breaks. PARP inhibitors inhibit DNA repair in cancer cells, so cells deficient in other DNA repair pathways, such as those seen with BRCA mutations, can be sensitive to PARP inhibitors eventually leading to cell death.”
From the BMN-673 trial description:
“BMN-673 has been proven to be highly active in mouse models of human cancer and also appears to be more selectively cytotoxic with a longer half-life and better bioavailability as compared to other compounds in development.”
“The poly ADP-ribose polymerase, or PARP, enzymes play a key role in DNA repair by detecting and initiating repair if a DNA strand breaks. Laboratory experiments have shown that, in tumor tissues with certain types of pre-existing DNA repair abnormalities, such as mutations in the BRCA1 and BRCA2 genes, inhibiting PARP enzymes results in greater cell death than in normal tissues. We are evaluating cancer patients whose malignancies have BRCA1 and BRCA2 mutations or other DNA repair deficiencies to determine whether their tumors are sensitive to PARP inhibition.”
Judy Garber said 20% of BRCA1 carriers do not seem to benefit from treatment with PARP inhibitors–their tumors have somehow mutated their way back to an active BRCA1 gene and thus don’t depend so much on the PARP pathway to fix DNA mistakes when replicating.
She also said as a class, the PARP inhibitors are more the same than different, so if one doesn’t work, it doesn’t make sense to try another one.