Overproduction of c-MYC was found to repress BIN1, which leads to higher levels of a DNA-repair enzyme.
The c-Myc oncoprotein has been found toplay a role in how cancer cells acquire resistance to DNA-damaging therpeutics. Researchers from Louisiana State University Health Sciences Center (LSUHSC) say that iInhibition of oncogenic c-MYC may provide an attractive strategy for cancer therapy in combination with DNA-damaging agents.
While scientists have known that cancer cells can acquire resistance to DNA-damaging therapeutics, the genetic mechanisms through which this occurs have remained unclear until now. A paper detailing at least some of those mechanisms will be published in the March 29 issue of Science Signaling.
The researchers studied resistance to the chemotherapy drug cisplatin. They found that the c-MYC oncoprotein decreases production of BIN1, a c-MYC inhibitor. BIN1 usually suppresses an enzyme essential for DNA repair. Thus the sensitivity of cancer cells to cisplatin depends upon BIN1 abundance. Overproducing the c-MYC oncoprotein repressed BIN1, blocking its life-saving action.
“Inhibition of oncogenic c-MYC may provide an attractive strategy for cancer therapy in combination with DNA-damaging agents,” says research team leader Daitoku Sakamuro, Ph.D., assistant professor of pathology at LSUHSC New Orleans and the LSUHSC Stanley S. Scott Cancer Center.
He and the research team add that analyzing the levels of the c-MYC and BIN1 proteins or their mutational status may also serve as a prognostic marker to determine whether a cancer will respond to an aggressive dose of therapeutic agents.Additionally, Dr. Sakarmuro will continue research to determine how malignant cancer cells can be resensitized to conventional DNA-damaging therapeutic agents.