Breast Cancer Tumor Cells Vulnerable to New Treatment Approach

The PI3K/AKT pathway may provide a new therapeutic target for breast cancer combination therapy.

Researchers have found the process of abnormal signaling through the PI3K/AKT pathway that helps drive the production of glutathione in breast cancer could present a new potential target for chemotherapy.

The adaptation of glutathione, a major cellular antioxidant, allows cancer cells to survive even in the presence of toxic chemotherapy.

A study published in Nature Cell Biology tested the efficacy of standard chemotherapy in combination with a drug that blocks glutathione production. The combinational therapy was used in the laboratory setting, as well as in mice.

The results of the study showed that the combination therapy caused significant regression of breast cancer with PI3K/AKT pathway mutations.

“These findings are important as they further highlight how targeting the specific metabolic requirements of cancer cells can prove effective in their selective eradication,” said researcher Pier Paolo Pandolfi, MD, PhD.

Additional research needs to be conducted to learn whether a specific glutathione production inhibitor could be developed that is safe for human use. Furthermore, researchers need to determine if enhanced glutathione production is also observed in tumors that harbor mutations other than those in the PI3K/AKT pathway.

The question also remains as to whether there are other antioxidant pathways in tumor cells that are controlled by the PI3K/AKT pathway in order to drive cancer.

“Our work has uncovered a vulnerability in human breast cancer that is used by tumor cells to escape the lethal effects of conventional chemotherapy and that leads to resistance to such therapies,” said researcher Alex Toker, PhD. “By targeting this vulnerability with specific drug combinations, the hope is that efficient therapeutic responses will be observed and with reduced toxicity.”