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

Daniel W Cole1, Peter F Svider1, Kerolos G Shenouda1

  • 1Department of Otolaryngology - Head and Neck Surgery, Wayne State University School of Medicine, Detroit, MI, USA.

Experimental Cell Research
|May 11, 2019
PubMed

Insights

Many anti-cancer drugs activate the unfolded protein response (UPR), a key pathway in cancer cell death. This review explores UPR

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • FDA-approved anti-cancer therapies frequently activate the unfolded protein response (UPR).
  • UPR signaling is critical for the apoptotic execution of cancer cells induced by various chemotherapeutic agents.
  • Despite its role in cancer, UPR is not currently an intended drug target in cancer therapy development.

Purpose of the Study:

  • To review existing literature on the role of the UPR in mediating chemotherapy-induced cell death.
  • To explore the UPR's involvement in squamous cell carcinomas of the head and neck (HNSCC) and oral cavity (OCSCC).
  • To focus on preclinical studies investigating UPR signaling in HNSCC and OCSCC.

Main Methods:

  • Comprehensive literature review of preclinical studies.
  • Analysis of research focusing on UPR activation by anti-cancer therapies.
  • Examination of UPR's role in HNSCC and OCSCC models.

Main Results:

  • Numerous preclinical studies demonstrate that various compounds can induce UPR signaling in diverse cancer models.
  • The UPR plays an essential role in driving the genesis and maintenance of the malignant phenotype.
  • Evidence suggests UPR activation contributes to chemotherapy-induced cell death in HNSCC and OCSCC.

Conclusions:

  • The unfolded protein response is a significant mediator of chemotherapy-induced apoptosis in head and neck cancers.
  • Targeting the UPR presents a potential therapeutic strategy for HNSCC and OCSCC.
  • Further preclinical research is warranted to fully elucidate and exploit the UPR's role in these cancers.
Keywords:
ER stressHNSCCHead and neck squamous cell carcinomaNatural productsOral cavity squamous cell carcinomaUnfolded protein response

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