Jenifer B. Gifford and Reginald Hill* Pages 701 - 708 ( 8 )
Background: Resistance to therapy is a major hindrance to patient survival in cancer, underscoring a critical need to elucidate the underlying mechanisms responsible for chemoresistance. Research has demonstrated that endoplasmic reticulum (ER) stress plays a significant role in allowing cells to survive conditions that would normally elicit cell death. Specifically, elevated expression of GRP78, the master regulator of the unfolded protein response (UPR), has been shown to induce chemoresistance and serves as a indictor of poor prognosis in patients.
Objective: Evaluating the expression of GRP78 and its downstream targets in a wide range of cancers may allow clinicians to predict resistance to a number of commonly used therapies. Moreover, understanding the mechanism(s) of action GRP78 uses to regulate chemoresistance will accelerate the development of more efficacious treatment strategies that target GRP78 to abrogate chemoresistance.
Results: This mini-review highlighted the roles of targets downstream of GRP78 and explored their mechanisms related to cellular survival. Furthermore, a summary of the connection between GRP78 expression and patient prognosis was provided. Lastly, strategies for targeting GRP78, in order to improve treatment efficacy, was explored.
Conclusions: GRP78 maintains an important role in regulating signaling pathways that control cell survival and this review draws attention to its value as a prognostic marker and therapeutic target.
Cancer, chemoresistance, ER stress, GRP78, unfolded protein response.
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46617, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46617