Diet fads that influence consumers to deprive their bodies of certain foods, such as the Atkins low-carb diet program, have been around for decades. While this can be a hit or miss for weight loss, scientists are finding the concept of nutrient deprivation may affect tumor growth. Depriving the tumors of cysteine, a non-essential amino acid that becomes essential only to tumor cells once they have been malignantly transformed, has been shown to shrink tumor cells.
Center for Genomic and Computational Biology (GCB) members Ashley Chi, Ph.D. and David Hsu, M.D., are collaborating to study this method to treat renal cell carcinomas. The team found that depriving cancer cells of cystine triggered a form of cell death called necrosis in mouse models of the disease.
In his lab, Hsu, a medical oncologist, generates patient-derived models of cancer and provides them to many Duke investigators who are interested in cancer research. “Ashley approached me to find out if we could use these models to study renal cell carcinomas,” said Hsu, “therefore, we combined his area of expertise in renal cell carcinoma with my expertise in generating patient-derived models of cancer in order to develop new and novel therapeutics.”
Chi and Hsu received a two-year, $600,000 grant from the Department of Defense in order to continue their research.
This DOD grant will allow Chi and Hsu to try different ways to induce cystine deprivation in mice in order to see what works to shrink or kill renal cell carcinomas. First, the pair will determine what the genetic determinant of the cystine addiction is, building on their existing research discussed in a previous study published by the journal Cancer Research. Most renal cell carcinomas are missing a VHL tumor-suppressor gene, which keeps healthy cells from developing into tumors. “Being able to identify the VHL tumor-suppressor gene is important,” Chi said, “because it allows us to more easily target the tumor.”
For now, the study will continue experiments in mouse models. If Chi and Hsu can continue to prove that cystine deprivation is responsible for shrinking tumors, they hope to begin clinical trials on human subjects.
In addition to renal cell carcinomas, the pair have also studied tumor cell cystine deprivation in a study surrounding a vicious, treatment-resistant form of breast cancer, triple negative breast cancer, and it’s response to cystine starvation. The results from both of these studies indicate that blocking cystine uptake may be an effective way of treating not only these two cancers, but other aggressive cancers as well.