A new approach to using PARP inhibitor therapy for triple negative breast cancer

Start Year: 2011
Finish Year: 2013
Chief Investigator: Professor Michael Friedlander
Grant Type: Novel Concept Awards
Institution: Prince of Wales Hospital and NHMRC Clinical Trials Centre

PARP inhibitors are a new class of drugs that exploit a weakness or ‘fatal flaw’ in inherited breast cancers as well as non-genetic breast cancers called triple negative breast cancers. These cancers have defective DNA repair, which is essential for cell survival and instead depend on PARP, an enzyme responsible for backup DNA repair. PARP inhibitors block this critical enzyme, which is fatal to cancer cells, but normal cells are spared as they still have the ability to repair DNA damage. This is an excellent example of targeted therapy where only the cancer cells are killed and normal cells spared. This is a major advance, but researchers are still learning how best to use these drugs and how to combine them with chemotherapy.

Combination has proven to be more difficult than expected due to its effect on reducing blood counts and has resulted in most trials reducing the dose and duration of administration of the PARP inhibitor while maintaining full doses of chemotherapy. This research group proposes a different and unique approach – rather than reduce the dose of the PARP inhibitors they will use a low dose of cyclophosphamide, which will increase DNA damage and thus hypothesise an increase in the effectiveness of the PARP inhibitor.