Researchers at the Medical University of South Carolina (MUSC) have found a way to target drug-resistant oesophageal cancer cells by exploiting the different energy needs of cancerous cells compared with healthy ones. This breakthrough paves the way for new treatments for an otherwise lethal cancer. These findings were published in Nature Communications.
Current figures by the American Cancer Society suggest that only 20% of patients diagnosed with oesophageal squamous cell carcinoma (ESCC) survive more than five years. This is because the condition tends to be diagnosed at a late stage, once the cancer has already spread to other parts of the body.
For the study, Shuo Qie, a postdoctoral fellow at MUSC Hollings Cancer Centre, and colleagues aimed to learn more the relevant the cancer-driving pathway discovered in previous research with a view to targeting it in treatment. This pathway, called the Cyclin D1 axis, is an intersection at which several cancer-promoting changes occur. The protein Fbxo4, which usually prevents cancer by controlling cyclin D1 degradation, no longer exerts its protective effects, allowing cells to spiral out of control.
Qie found that the axis activates a metabolic switch that causes ESCC cells to depend much more on glutamine than glucose. Healthy cells break down both glucose and glutamine for their energy needs, but ESCC cells preferentially use glutamine.
This means that glutaminase inhibitors could serve as a potential new therapy for ESCC. Researchers tested the efficacy of a combination regimen that included a glutaminase inhibitor and metformin in cancer cell lines and mice. The treatment was effective in cancer cells, including those resistant to other therapies. The research team are hoping to conduct clinical trials for their combination treatment in order to take these findings forward.