Scientists Find and Stop Energy Source for Cancer Cells

Researchers target cell division to prevent the growth and spread of cancer.

Of great importance to the oncological world is the development of therapies that target certain stages of cancer development.

A new study by the Spanish National Cancer Research Center Cell and National Cancer Unit has revealed yet another target for immunotherapies, proving that blocking glycolysis is especially damaging to the division of cancer cells. Targeting this process in combination with chemotherapeutic agents such as taxol is thought to be an effective treatment for cancer.

Glycolysis is the molecular mechanism that makes it possible to extract energy from glucose. By starving cancer cells of glucose, they are effectively and efficiently killed off. The process seems simple enough and scientists seem optimistic about its treatment potential.

Cancer is defined by the rapid, uncontrolled proliferation of cells. It is the goal of scientists to find ways to interrupt cell division so that cancer does not grow and spread throughout the body.

“There are many therapeutic agents today, such as taxol, that precisely prevent the division of cancer cells by interrupting the mitosis (an especially delicate part of the cell division process in which the genetic material is passed from the mother cell to the daughter cells),” said Maria Salazar Roa, CNIO researcher and co-director of the study.

A topic of debate among scientists is the mechanism through which cancer cells obtain their energy. Using molecular biology and biochemistry techniques, the authors describe how the AMPK and PFKFB3 proteins become significantly active during mitosis, leading cell metabolism towards glycolysis.

“These proteins detect damage to the mitochondria (the cell’s energy sources) in response to cell division and make the energy depend mainly on glucose,” said Elena Domenech, whose signature appears first on the paper that she has been preparing as her doctoral thesis.

Scientists analyzed how much glucose is required for cancer cells treated with taxol and, therefore, when mitosis is interrupted.

“We can see that antimitotic treatments, such as taxol, increase the need cancer cells have for glucose even more than when there is no treatment,” said Salazar.

Seeing as cancer cells need more glucose when they are being treated with taxol, scientists conclude that the prevention of glycolysis should enhance the anti-cancer effect of antimitotic drugs.

In effect, this increases cancer cells’ need for glucose while taking away the ability for glycolysis to take place. The cancer cells essentially die of starvation as it is unable to obtain the energy it needs to cover its vital functions.

Through observing breast cancer models in mice, scientists ascertained that mitotic drugs such as taxol are more efficient when the cells’ ability to metabolize glucose is eliminated using PFKFB3 inhibitors.

“The therapeutic value of inhibiting PFKFB3 has often been discussed; however, no appropriate cell-based scenario had been proposed for its clinical use. Our results suggest that PFKFB3 inhibitors can be extremely efficient in combination with antimitotic drugs,” said Marcos Malumbres, group leader at CNIO.

The next step for scientists is to determine how effective this development would be regarding the treatment of other tumors, such as lymphoma and melanoma. In cutting off the energy source of cancer cells, scientists plan to make significant strides in the world of oncology using this method.