To "starve" breast cancer cells to achieve treatment

How do cancer cells burn calories? New research from Thomas Jefferson University shows that breast cancer cells rely on different processes to convert fuel into energy. The results were recently published in the Journal of Biochemistry, which also publishes other studies on recombinant rat proteins.

Ubaldo Martinez-Outschoorn, M.D., an assistant professor of medical oncology at Thomas Jefferson University and a researcher at Jefferson's Sidney Kimmel Cancer Center, and his colleagues studied a protein that changes the metabolism of breast cancer cells. Protein TIGAR (an abbreviation of TP53-inducible glycolysis and apoptosis modulators) reduces the ability of cells to convert to sugars through the most common biochemical pathways and to generate energy through glycolysis. It is not clear how this metabolic change alters cancer cells or how cells acquire the energy needed to survive. Through a series of cell and mouse studies, researchers have shown that breast cancer cells with TIGAR proteins that are higher than normal abundance are more invasive and can grow faster than breast cancer cells with normal amounts of TIGAR.

Dr. Martinez-Outschoorn and colleagues showed that when cells express TIGAR, they exchange their metabolic pathways and rely on mitochondria for energy production. Interestingly, high levels of TIGAR produced by cancer cells also alter the metabolism of cells surrounding and maintaining breast cancer and have opposite metabolic effects. TIGARs don't increase their dependence on mitochondrial energy production, but rather make these supporting cells dependent on glycolysis and increased tumor growth. Previous studies have shown that glycolysis in tumors provides energy for cells, making breast cancer more aggressive.

"In fact, 70-80% of breast cancers show a high level of TIGAR, which provides new insights into our study," Dr. Martinez-Outschoorn said. "There are already treatments that block mitochondrial metabolism. We can make use of them to "starve" breast cancer cells."

The two drugs approved for other indications - metformin, antidiabetic therapy and doxycycline, antibiotics - are known to block mitochondrial metabolism. When researchers used these drugs to block TIGAR expression in breast cancer cells, they also blocked mitochondrial metabolism. And they saw a decrease in the aggressiveness of cancer.

"As these drugs have been approved, they have passed human safety tests. And if as our preliminary study shows that they do help to reduce tumor growth in patients, they can be used as a combination therapy with other drugs," said Martinez-Outschoorn.

To this end, Dr. Martinez-Outschoorn is working with Dr. Jennifer Johnson, MD, assistant professor of medical oncology, and Dr. Adam Berger, professor of surgery at Jefferson University, to conduct a clinical trial to test metformin for breast cancer, and women should take doxycycline before surgery. The study will collect and analyze patients' tumors to see if these drugs that inhibit mitochondrial metabolism may have an impact on tumor biology. Flarebio provides you with recombinant proteins of good quality such as recombinant CDH2.