Iok In (Christine) Chio, Ph.D.

Historically, antioxidant supplementation has been viewed as an effective prevention strategy against cancer. Despite this, there is growing evidence that antioxidants support cancer growth and lead to worse patient survival. These findings have changed the way we view antioxidants and the treatment of cancer. This is particularly true in a subset of cancers that are driven by an oncogene called KRAS, which can directly engage an antioxidant program to promote survival in cancer cells. The KRAS oncogene is frequently activated by mutations in pancreatic, colon and lung cancers. However, it has proven extremely difficult to find new drugs that directly inhibit activated KRAS. Currently, patients diagnosed with these cancers are given chemotherapy which also have many side effects due to their general toxicity. Thus, the creation of new therapies which specifically target cancer cells, while sparing other normal, healthy cells, has the potential to increase patient survival while improving their quality of life during therapy. Our laboratory has found that the production of antioxidants by NRF2 is essential for the growth and survival of KRAS-mutant cancer cells. To understand how antioxidants are made and used by cancer cells, we use organoid models—cells grown in three- dimensions to study the role of NRF2 in KRAS-mutant cancers. These results will lead to the creation of new therapies which selectively target cancer cells while sparing healthy cells of the body, leading to better patient health and survival.