Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep-Oct;28(5):401-406.
doi: 10.1097/PPO.0000000000000620.

STING Agonists in Head and Neck Squamous Cell Carcinoma

David G Wallington  1 , Joseph N Contessa, Thomas J Hayman
Affiliations
Review

STING Agonists in Head and Neck Squamous Cell Carcinoma

David G Wallington et al. Cancer J. 2022 Sep-Oct.

Abstract

Despite the development of new treatment paradigms and improved biologic understanding of head and neck squamous cell carcinoma (HNSCC), therapeutic resistance remains a substantial problem, and novel treatment approaches are needed. Stimulator of interferon genes (STING) is a critical regulator of the antitumor response through regulation of both immune-dependent and tumor-intrinsic mechanisms. As such, the STING pathway has emerged as a rational pharmacologic target leading to the development of multiple STING agonists. These compounds have impressive preclinical efficacy as single agents and with PD-1 (programmed death-1) axis agents. However, clinical evaluation in this context has yet to show substantial efficacy. In contrast to monotherapy approaches, activation of STING in combination with DNA-damaging agents has been shown to enhance the effect of these agents in preclinical models and represents a promising approach to improve outcomes in patients with HNSCC. In this review, we will discuss the preclinical and clinical data supporting the use of STING agonists and highlight potential avenues of exploration to unlock the potential of these agents in HNSCC.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

References

    1. Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455:674–678.
    1. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11:373–384.
    1. Burdette DL, Monroe KM, Sotelo-Troha K, et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011;478:515–518.
    1. Sun L, Wu J, Du F, et al. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339:786–791.
    1. Shekarian T, Valsesia-Wittmann S, Brody J, et al. Pattern recognition receptors: immune targets to enhance cancer immunotherapy. Ann Oncol. 2019;30:2017.

MeSH terms