The cytosolic DNA-sensing cGAS–STING pathway in cancer

J Kwon, SF Bakhoum - Cancer discovery, 2020 - AACR
Cancer discovery, 2020AACR
The recognition of DNA as an immune-stimulatory molecule is an evolutionarily conserved
mechanism to initiate rapid innate immune responses against microbial pathogens. The
cGAS–STING pathway was discovered as an important DNA-sensing machinery in innate
immunity and viral defense. Recent advances have now expanded the roles of cGAS–
STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to
drive tumorigenic behaviors. In this review, we discuss the link between the cGAS–STING …
Abstract
The recognition of DNA as an immune-stimulatory molecule is an evolutionarily conserved mechanism to initiate rapid innate immune responses against microbial pathogens. The cGAS–STING pathway was discovered as an important DNA-sensing machinery in innate immunity and viral defense. Recent advances have now expanded the roles of cGAS–STING to cancer. Highly aggressive, unstable tumors have evolved to co-opt this program to drive tumorigenic behaviors. In this review, we discuss the link between the cGAS–STING DNA-sensing pathway and antitumor immunity as well as cancer progression, genomic instability, the tumor microenvironment, and pharmacologic strategies for cancer therapy.
Significance
The cGAS–STING pathway is an evolutionarily conserved defense mechanism against viral infections. Given its role in activating immune surveillance, it has been assumed that this pathway primarily functions as a tumor suppressor. Yet, mounting evidence now suggests that depending on the context, cGAS–STING signaling can also have tumor and metastasis-promoting functions, and its chronic activation can paradoxically induce an immune-suppressive tumor microenvironment.
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