FAIRHOPE, Ala. — Researchers at the University of South Alabama Mitchell Cancer Institute (MCI) have discovered that the growth of breast cancer cells can be slowed by thwarting an enzyme pathway that produces cellular energy needed by the disease. The findings have been published online by the leading cancer research journal, Oncogene.

Otto Warburg, a German scientist and Nobel laureate, discovered nearly 80 years ago that normal cells depend on a process that consumes oxygen and glucose to make energy. Cancer cells, however, are more reliant on sugar metabolism, known as glycolysis.

Cancer cells consume far more sugar than normal cells to maintain sufficient energy supplies, according to researchers, and they become addicted to glycolysis.

Recent studies found this unique property is an Achille’s heel for cancer cells. By understanding the unique energy demands of cancer cells, the MCI scientists believe drugs may be designed to target this weakness.

It all seems like a relatively simple solution to a rather complicated problem.

“Actually, cutting off the energy supply to living cells is not difficult,” said Dr. Ming Tan, assistant professor of oncologic sciences, Vincent F. Kilborn Jr. Cancer Research Scholar and leader of the MCI research team that made the discovery. The real difficulty is to selectively cut off the energy supply of cancer cells and to spare the normal cells.”

He explained that Warburg’s initial discovery would have borne significant fruit years ago, but because of the lack of knowledge of molecular biology and a technology limitation at the time of the German’s research, the mechanism of glycolysis was unknown, and there was no good method to block the specific enzyme pathways of glycolysis.

Tan said, “Recently researchers have found that cancer cells benefit from the switch of energy supply to glycolysis, and molecular advances in this area have revealed that we may exploit the cancer cell’s ‘sweet tooth’ for cancer therapy.”

It’s too soon to tell how long it might take for the new discoveries to produce a silver bullet that helps fight all forms of breast cancer, but they hold promise.

“Recent studies found that the activation of tumor-promoting genes is one of the reasons for the switch of energy supply of cancer cells,” Tan said. “In our study we used an experimental model that has activation of tumor promoting gene ErbB2, which happens frequently in breast cancer cells. This is why our findings are particularly meaningful for breast cancer.

He added, “Warburg effect is a common feature of most cancer cells. Although we used a breast cancer model with activation of tumor-promoting gene ErbB2, the insight we gained through studying this model system should also have implications to other tumor promoting genes-mediated glycolysis.”

Tan said the research is still in early pre-clinical study stage. It was conducted in the laboratory using cancer cells.

Animal studies and human sample tests are needed before it can be put into practical use in patients, and that stage is expected to begin soon.

“Cancer metabolism has emerged as one of the most exciting areas of cancer research that may open a new therapeutic avenue and may bring new hope for cancer patients,” Tan said. “The pre-clinical studies may lead to translation into clinical trial and may ultimately benefit many cancer patients in the future.”

He said there are currently a few sugar metabolism inhibitors under pre-clinical study, such as 2-DG, which are given to animals orally. Other forms of the treatment may be developed depending on the individual properties of the specific therapeutic agents.

Others working alongside Tan on the research are Drs. Yuhua Zhao, Ming Zhou, Hao Liu, Yan Ding, Hung Khong and Oystein Fodstad.

This MCI study was funded through the Vincent F. Kilborn Jr. Cancer Research Foundation at USA and the Radiumhospitalets Legater of the University of Oslo in Norway. Tan said the team is grateful for the generous support.

Tan came to the University of South Alabama two years ago, and began working on the research project after completing studying literature on cancer metabolism for two years.

Asked what is next on his radar, he said, “The emphasis of our research is on signal transduction pathways regulating the malignant behavior of tumor cells. Currently we focus on growth factor receptors, such as HER-2/ErbB2, mediated signal transduction, cancer metabolism, metastasis, resistance to therapeutic agents and targeted therapy for cancer using human breast cancer as a model system. Our ultimate goal is to translate the knowledge acquired in the laboratory into future novel therapeutics.”