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.