Most of you have probably heard of the BRCA 1 and BRCA2 gene mutations, that can predispose patients with mutations of these genes to breast, ovarian and other cancers. BRCA1 and BRAC2 are proteins that play a key role in the repair of damage in the double stranded DNA of cells. When there is a mutation in one of the BRCA genes, cells are especially vulnerable to inhibition of a second type of DNA repair that repairs single strand “nicks” in the DNA that requires an enzyme called PARP (Poly ADP ribose polymerase). Two investigational products are currently in phase 1 and phase 2 clinical trials for use in patients with advanced cancer. The two drugs currently in studies are olaparib owned by Astra Zenica and BSI-201 owned by Sanofi Aventis. Up to this point the PARP inhibitors have been most promising in patients with BRAC mutations, and are furthest along in advanced breast cancer patients. The hope is that these drugs will enhance the effect of chemotherapy by preventing the cells damaged by the chemotherapy from repairing their DNA damage and surviving.
The PARP drugs so far have been well tolerated and seem to have few serious side effects. Cheers to out to our bench scientists doing basic science for discovering these DNA repair pathways, and taking that knowledge and using it to develop yet another promising class of drugs. I have a vested interest in these trials as my wife has a BRCA2 gene mutation and is getting treatment for advanced ovarian cancer, so stay tuned for any further advances in studies on these new drugs.
Anyone who has an opinion about this please comment. I have just the knowledge I can find from reading, and it looks like PARP inhibitors have shown most promise in hormone receptor negative tumors, but I have seen nothing about this particular issue. Dr.P.
Will parp inhibitors be less effective if a patient has stage 4 breast cancer that is her-2 positive, but no progesterone and no estrogen receptors? Why?