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Review
. 2019 Sep 1;382(1):111386.
doi: 10.1016/j.yexcr.2019.04.007. Epub 2019 May 7.

Targeting the unfolded protein response in head and neck and oral cavity cancers

Daniel W Cole  1 , Peter F Svider  1 , Kerolos G Shenouda  1 , Paul B Lee  2 , Nicholas G Yoo  1 , Thomas M McLeod  1 , Sean A Mutchnick  1 , George H Yoo  3 , Randal J Kaufman  4 , Michael U Callaghan  5 , Andrew M Fribley  6
Affiliations
Review

Targeting the unfolded protein response in head and neck and oral cavity cancers

Daniel W Cole et al. Exp Cell Res. .

Abstract

Many FDA-approved anti-cancer therapies, targeted toward a wide array of molecular targets and signaling networks, have been demonstrated to activate the unfolded protein response (UPR). Despite a critical role for UPR signaling in the apoptotic execution of cancer cells by many of these compounds, the authors are currently unaware of any instance whereby a cancer drug was developed with the UPR as the intended target. With the essential role of the UPR as a driving force in the genesis and maintenance of the malignant phenotype, a great number of pre-clinical studies have surged into the medical literature describing the ability of dozens of compounds to induce UPR signaling in a myriad of cancer models. The focus of the current work is to review the literature and explore the role of the UPR as a mediator of chemotherapy-induced cell death in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC), with an emphasis on preclinical studies.

Keywords: ER stress; HNSCC; Head and neck squamous cell carcinoma; Natural products; Oral cavity squamous cell carcinoma; Unfolded protein response.

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Conflict of interest statement

Conflicts of interest

None.

Figures

Fig. 1.
Fig. 1.
Overview of the protein translation during homeostasis and malignancy(A) and the UPR hypothesis (B).
Fig. 2.
Fig. 2.
Overview of ER stress and the UPR highlighting the apoptotic (PERK-eIF2α-ATF4-CHOP) and adaptive (IRE1α-XBP1) axes.
See this image and copyright information in PMC

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