Obtaining a genetic picture of how a tumor will react to the many treatment techniques available could help doctors prescribe therapies customized for individual cancer patients' needs, suggests a Purdue University research team.
A group of scientists including Jian-Jian "J.J." Li has found a trio of proteins often present in cancer cells that protect the tumor from destruction by radiotherapy. Because no single protein in the group is responsible for keeping the cancer alive, Li said that the key to a successful assault could rest in a deeper understanding of the relationship among these protein molecules – an understanding that could be made available through genetic testing.
"We have discovered that breast cancer cells defend themselves on the molecular level against radiation, and this response could be reducing the effectiveness of modern medicine's fight against cancer," said Li, who is an associate professor of health sciences in Purdue's School of Health Sciences. "Because these three proteins interact in ways peculiar to each tumor, it might help doctors to first obtain the 'genetic fingerprint' of cancerous tissue in order to find out which treatment method will be most effective."
The research appears in this week's issue of the Journal of Biochemistry. Li's co-authors include researchers from the City of Hope National Medical Center, Bio-Rad Laboratories and the National Institutes of Health.
All living cells are kept alive through the efforts of thousands of different proteins, each of which may have many different and interrelated functions. Proteins are brought into action, or "expressed," by genes in the cell's DNA when certain needs arise – such as reproduction or metabolizing energy. Three such proteins found in most human cells have been the focus of Li's research for several years, each of which is commonly known to scientists by a technical name: ERK, NF-kappa B and GADD45 beta.
"In healthy cells, these three proteins all play a role in building new cellular structures, allowing the body to grow and regenerate," Li said. "Each has individual functions that are well known. NF-kappa B and ERK, for example, work as construction managers that tell the genes where more building blocks are needed and how they should be arranged, while GADD45 beta helps repair damage to DNA. This helps keep a cell from mutating as it grows."
NF-kappa B beta is known to be present in abnormally high amounts in tumors. However, scientists also have noticed that after the NF-kappa B has been inhibited, the cancer cells are less responsive to radiotherapy. Apparently, Li said, the presence of the protein keeps tumor cells alive despite receiving a punishing amount of radiation that ordinarily would kill them.
"Previous research has also implicated NF-kappa B in this type of radioresistance to cancer," Li said. "No one really knew what was happening. But the issue needed resolution because, once again, we were confronting the standard dilemma in cancer treatment: How do you destroy the cancer without damaging the surrounding healthy cells?"