Old dogs, new trick: classic cancer therapies activate cGAS

• Published in: Cell research Vol. 30; no. 8; pp. 639 - 648
• Main Authors: Yum, Seoyun, Li, Minghao, Chen, Zhijian J.
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-08-2020; Nature Publishing Group
• Subjects: 38; 631/250/262; 631/67/327; 96; AMP; Antitumor activity; Biomedical and Life Sciences; Cancer; Cancer therapies; Cell Biology; Cell death; Cellular Senescence; Chemotherapy; Cyclic GMP; Deoxyribonucleic acid; DNA; DNA Damage; Enzyme Activation; Humans; Immune response; Immune system; Immunity, Innate; Immunosurveillance; Immunotherapy; Interferon; Life Sciences; Membrane Proteins - metabolism; Neoplasms - enzymology; Neoplasms - immunology; Neoplasms - therapy; Nucleotidyltransferases - metabolism; Radiation therapy; Review; Review Article; Stimulators; Surveillance; Tumorigenesis
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/s41422-020-0346-1

The discovery of cancer immune surveillance and immunotherapy has opened up a new era of cancer treatment. Immunotherapies modulate a patient’s immune system to specifically eliminate cancer cells; thus, it is considered a very different approach from classic cancer therapies that usually induce DNA damage to cause cell death in a cell-intrinsic manner. However, recent studies have revealed that classic cancer therapies such as radiotherapy and chemotherapy also elicit antitumor immunity, which plays an essential role in their therapeutic efficacy. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the downstream effector Stimulator of Interferon Genes (STING) have been determined to be critical for this interplay. Here, we review the antitumor roles of the cGAS-STING pathway during tumorigenesis, cancer immune surveillance, and cancer therapies. We also highlight classic cancer therapies that elicit antitumor immune responses through cGAS activation.