Activation of the cGAS-STING pathway, involving cytosolic DNA sensing and induction of a type I IFN response, promotes potent antitumor effects and is part of the mechanism of action of various anticancer therapeutics. But, cGAS-STING induced inflammation can also mediate tumor growth and metastasis in a tumor type- and tumor stage-specific manner. Ng et al. review the dichotomous role of this pathway in cancer and how it can be adapted for therapeutic use.
cGMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS-STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS-STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.
Author Info: (1) Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada; These authors contributed equally to this work. (2) Department of Integrative Oncology, BC Cancer Agenc
Author Info: (1) Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada; These authors contributed equally to this work. (2) Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada; These authors contributed equally to this work. (3) Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada. (4) Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada. Electronic address: wanlam@bccrc.ca.
