Endoplasmic Reticulum (ER) stress response proteins are overexpressed in cancer cells, and are often associated with high resistance to chemotherapy and poor prognosis, shows a review article by a research team from the Hill Lab at the University of Notre Dame.
Innate or acquired resistance to current standard-of-care therapies is a major hindrance to successful chemotherapeutic intervention. There is a critical need to elucidate the underlying mechanisms responsible for chemoresistance in order to accelerate the development of more efficacious treatment strategies.
ER stress response proteins are produced by cells undergoing periods of stress and facilitate the folding of proteins. Elevated expression of GRP78, the master regulator of the unfolded protein response, has been shown to induce chemoresistance and serves as an indicator of poor prognosis in patients with a variety of cancers.
Elevated GRP78 expression has been linked to the failure of a growing number of current standard-of-care therapies, which suggest that it is necessary to identify strategies to inhibit GRP78 function in order to sensitize chemotherapy-resistant tumors to currently available treatment regimens.