You may have heard the very exciting data about patients with breast cancer who carry BRCA mutations. These mutations indicate a genetic predisposition for breast cancer.
The function of BRCA is DNA repair, very similar to the genes associated with familial colorectal cancer known as Lynch syndrome or HNPCC (hereditary nonpolyposis colon cancer) which are the DNA mismatch repair genes.
Over the last couple of years novel drugs have been developed which are called PARP inhibitors. PARP is involved in DNA repair too. Tumors which have some DNA repair deficiencies which are treated with PARP inhibitors seem to be particularly vulnerable to this specific therapy. PARP inhibitors attack the weakness of these tumors which are impaired in DNA repair.
Usually this gives tumors a potential advantage creating more and more aggressive mutations which are not repaired, but now we have a special smart weapon.
At this year’s American Society for Clinical Oncology meeting, PARP inhibitors showed very promising anti-tumor efficacy. Since colon cancer which is based on HNPCC or DNA mismatch repair mutations may be also more sensitive against these drugs, we have developed new clinical trials.
At the University of Southern California, we just opened a phase II trial for colon cancer patients with MIN, known as microsatellite instability, which is a landmark sign for DNA mismatch repair. We are testing a novel compound from AstraZeneca and are hoping for similar exciting results as we have seen for breast cancer.
My colleagues in breast cancer are running a number of trials using the ABT888, the PARP inhibitor from Abbott alone or in combination with chemotherapy. Since there are data that these drugs may further increase efficacy of particular cytotoxic drugs.
We are getting closer and closer to a personalized chemotherapy, testing tumors for genetic switches to select more likely effective therapies. This trial is open for accrual at USC and other institutions including Vanderbilt, New York University, and sites in Denver, Palms Springs and Miami. Call the C3 Answer Line at 877-427-2111 for more information.
July 27, 2009 at 8:06 am, carla vannuci said:
Is it true that nicotinamide is a Parp inhibitor?
thanks
caregiver
July 27, 2009 at 11:17 am, Heinz Josef Lenz said:
When i remember right it is a weak inhibitor and was used in some of the early research studies and experiment. THe problems is that such high concentrations was needed that it becomes complicated to evaluated whether the effects seen was related to PARP inhibitory activity. Hope this helps. HJL