The first targeted therapy for a type of advanced, genetically based breast cancer is now available for US women after the Food and Drug Administration (FDA) expanded the indications for an existing cancer agent called Lynparza.
Patients with metastasized cancer (cancer that has spread) and an underlying inherited mutation to either of the BRCA tumor suppressor genes (BRCA+) are candidates for Lynparza (generically called olaparib), which was previously approved to treat select ovarian cancers mediated by BRCA.
“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” said Dr Richard Pazdur, director of the FDA’s Oncology Center of Excellence, in a statement. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”
In a randomized clinical trial of 302 BRCA+ patients, those who received Lynparza went an average of 7 months without disease progression compared to 4.2 months for those given chemotherapy alone.
The drug works by inhibiting an enzyme found in cell nucleuses, called PARP (poly ADP-ribose polymerase), that's involved in repairing damaged DNA. When this self-regulating machinery is blocked, attempts to fix naturally occurring "nicks" in the genetic code of each cell are halted or slowed, leading to more serious DNA strand breakage.
This is where genes like BRCA1 and BRCA2 normally come in: Their role is to fix double-stranded DNA breaks before dangerous mutations can take effect. Individuals with dysfunctional BRCA proteins are at higher risk of developing cancer from this unrepaired random damage, particularly in breast and ovarian tissue. According to the FDA's statement, approximately 5 to 10 percent of patients with any type of breast cancer have a genetic anomaly in their BRCA genes.
With one of the key double-stranded repair processes out of commission, the cells of BRCA+ patients rely more on PARP-mediated cellular repair to keep everything running smoothly. When this process is eliminated, through an inhibitor like Lynparza, the cancer cells (already messed up, but not messed enough up to die) are finally messed up enough to die. Phew.