The Unfolded Protein Response as a Therapeutic Target for Head and Neck Squamous Cell Carcinoma

Garshott, Danielle M.; Bechler, Shelby A.; Burchhardt, Daniela M.; O’Brien, Priyanka Shah; Yoo, George H.; Chiego, Daniel J.; Rehman, Aasia O.; Callaghan, Michael U.; Fribley, Andrew M.

doi:10.1007/978-3-319-27647-2_10

Cited by 6 publications

(12 citation statements)

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“…The "UPR Hypothesis" in cancer, as discussed previously [11], is predicated on the idea that high levels of UPR biomarkers present in cancer cells (e.g., GRP78/BiP, CHOP, eIF2α and eIF4e) ( Fig. 1A) can be pharmacologically leveraged against the tumor [11] (Fig. 1B).…”

Section: Introductionmentioning

confidence: 99%

“…The targeted activation of the unfolded protein response (UPR) as a selective approach to ameliorating malignancy has recently been discussed by our group and others for a wide variety of cancers [11][12][13][14][15][16][17]. The "UPR Hypothesis" in cancer, as discussed previously [11], is predicated on the idea that high levels of UPR biomarkers present in cancer cells (e.g., GRP78/BiP, CHOP, eIF2α and eIF4e) ( Fig. 1A) can be pharmacologically leveraged against the tumor [11] (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Increased GRP78/BiP expression is known to provide chemoresistance and is a biomarker for poor prognosis [20][21][22][23][24]. GRP78/BiP inhibition could also potentially interfere with angiogenesis by limiting the expression of vascular endothelial growth factor (VEGF) [19,25,26]. Another recent study reported that siGRP78 reduced clonogenicity and the self-renewal or "stemness" of progenitor cells in pancreatic cancer cells [27].…”

Section: Introductionmentioning

confidence: 99%

“…Increased UPR signaling has been demonstrated in vitro and in vivo models of HNSCC and OCSCC and represents a potential therapeutic target [11,[30][31][32][33][34]. Increased protein demand in malignant cells, fueled by the need to synthesize membrane proteins, signaling molecules, and to produce factors that assist in immune evasion and proliferation, can overwhelm the homeostatic folding capacity of the ER and lead to a chronic UPR.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the epithelial to mesenchymal transition activates the UPR (PERK-eIF2α) and sensitizes cells to ER stress [35]. Many studies have suggested that targeting cells with increased basal levels of UPR signaling through upregulation of pro-apoptotic pathways might be an effective therapeutic strategy [11,[36][37][38].…”

Section: Introductionmentioning

confidence: 99%

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

Cole

Svider

Shenouda

et al. 2019

Experimental Cell Research

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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.

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Section: Introductionmentioning

confidence: 99%