A powerful new breast cancer treatment could result from packaging one of the newer drugs that inhibits cancer's hallmark wild growth with another that blocks a primordial survival technique in which the cancer cell eats part of itself, researchers say.
While they are powerful killers of some breast cancer cells, new drugs called histone deacetylase inhibitors, or HDAC inhibitors, also increase self-digestion, or autophagy, in surviving, mega-stressed cells, Medical College of Georgia Cancer Center researchers reported during the Molecular Targets and Cancer Therapeutics International Conference this week in Boston. The conference is sponsored by the American Association for Cancer Research, the National Cancer Institute and the European Organisation for Research and Treatment of Cancer.
"To meet the energy demands of growth and survival, cancer cells start eating up their own organelles, so that surviving cells become dependent on this autophagy," says Dr. Kapil Bhalla, director of the MCG Cancer Center.
"By also using autophagy inhibitors, we pull the rug out from under them. The only way out is death," he says.
Researchers showed the potent HDAC inhibitor panobinostat's impact on autophagy in human breast cancer cells in culture as well as those growing in the mammary fat pads of mice. When they added the anti-malaria drug chloroquine, which inhibits autophagy, breast cancer kill rates increased dramatically.
"As breast cancer is growing, it's developing these mechanisms of resistance to death," says Dr. Bhalla, Cecil F. Whitaker, Jr., M.D./Georgia Research Alliance Eminent Scholar in Cancer and Georgia Cancer Coalition Distinguished Cancer Scholar. "What we are saying is there is a new way to affect a resistant population."
Fundamentals of survival and growth put a lot of stress on cancer cells. Their drive for both comes from the activation of oncogenes and loss of tumor suppressor genes that leaves cells looking desperately for ways to support their marching orders. Much like the extreme measures plane crash victims may take while stranded on a frozen mountaintop, autophagy becomes a survival strategy for the most stressed out cancer cells.