Washington: Researchers have discovered that cell metabolism plays an important role in the ability of cells to start a survival program called autophagy, an unwanted side effect of some anti-cancer drugs that help some tumor cells dodge treatment and eventually regrow into new tumours.
The findings provide new insights into ways to use cell metabolism to "pull the plug" on tumor cells that survive treatment, possibly leading to better treatments and outcomes for patients.
Research assistant professor Carol Mercer said, "Cells adapt to nutrient starvation by increasing autophagy, where a cell basically eats itself and recycles cellular contents to support essential processes until nutrients become plentiful once again. This process is regulated by the mammalian target of rapamycin (mTOR) and AMP-activated protein kinases (AMPK)."
Mercer, principal investigator on the study, and her lab worked primarily in cultured cells to understand how metabolism regulates autophagy, identifying strategies to manipulate this pathway to the patients' advantage.
This work was built on pre-clinical studies in animal models by Hala Elnakat Thomas, PhD, first author and research instructor in the department, who found that the combination of mTOR inhibitors were effective in the treatment of hepatocellular carcinoma (liver cancer) but had the potential disadvantage of increasing autophagy.
"Our data reveal the dynamic and metabolic regulation of autophagy and suggest new therapeutic strategies for cancer, neurodegenerative and mitochondrial diseases," Mercer says. "We need to further explore the reasons this occurs and the implications for how the metabolic regulation of autophagy can be used in the clinic."
The full findings are present in the journal Cell Reports....