Targeting redox status and mRNA translation in pancreatic cancer

Among the reasons that pancreatic cancer has a poor prognosis are the lack of effective treatments and the cancer cells’ development of drug resistance. Almost all pancreatic cancer cases are driven by mutations in a protein called KRAS, but there is not currently a treatment strategy to directly block the activity of KRAS. During her postdoctoral studies, Dr. Chio focused on a protein called NRF2, which is a transcription factor. Transcription factors influence the cells’ ability to translate genetic information in DNA and RNA into activated proteins that bring about the cells’ cancer-like abilities. She and her colleagues discovered that pancreatic cancer cells, in the presence of mutant KRAS, depend on the activity of NRF2. However, like KRAS, NRF2’s activity cannot currently be blocked by a treatment strategy. Dr. Chio found that NRF2 is involved in controlling a process called oxidation, through which cells react to low oxygen conditions that are typical of the pancreatic cancer cells’ environment. She therefore proposes to utilize organoids, or three-dimensional laboratory models of pancreatic cancer and its surrounding tissue, to better understand how NRF2 controls protein expression through regulating the process of oxidation. The research team will also explore whether oxidative regulation of protein synthesis could be leveraged to stop or slow the tumor’s growth. These results will serve as the basis for future clinical investigations of new drugs to target the protein synthesis processes in pancreatic cancer patients.