New medication, consisting of a blend of a protein inhibitor and traditional anticancer drugs, being developed to treat ovarian and breast cancer has been found to be effective, say researchers.
The finding has appeared in a new review for Faculty of 1000 Biology Reports.
Susan Bates and Christina Annunziata analysed numerous recent papers on this form of treatment, which takes advantage of the synthetic lethality of BRCA (breast cancer susceptibility genes) and poly-ADP ribose polymerase (PARP) proteins to attack cancerous cells even as it spares healthy ones.
BRCA and PARP are two major players in DNA repair and have different but complementary functions in the cell. Loss of the BRCA protein allows the cell to survive but greatly enhances its chances of becoming cancerous through the accumulation of mutations. However, the loss of both proteins kills the cell in a process called synthetic lethality.
The use of drugs to block the activity of PARP in cells missing BRCA, such as those found in certain breast and ovarian cancers, can spare healthy, non-cancerous cells because they have functional BRCA and are not affected by the loss of PARP. Thus, only cancer cells without functional BRCA protein are killed by drugs that inhibit PARP.
Recent clinical trials have demonstrated that cancers caused by mutations that knock out BRCA activity can be controlled by blocking PARP activity with specific drugs. Patients were treated with traditional anticancer drugs alone or in combination with one of two new PARP inhibitors, olaparib or BSI-201.
Bates points out that patients on combination therapy had improved "[disease] progression-free survival, and overall survival" as compared to patients treated with traditional drugs alone.
Bates is positive about the promise of combining PARP inhibitors with existing cancer drugs. She says that the results of these clinical trials "have provided proof of principle in achieving synthetic lethality" with PARP-inhibiting drugs and that treatments combining novel PARP inhibitors with traditional chemotherapeutic drugs have the potential to vanquish BRCA-associated breast and ovarian cancers.