Targeting STING in cancer: Challenges and emerging opportunities

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key pathway through which the host regulates immune responses by recognizing cytoplasmic double-stranded DNA of abnormal origin, and it plays an important role in tumor growth as well as metastasis, with relevant molecular details constantly being explored and updated. The significant immunomodulatory effects make STING an attractive target for cancer immunotherapy, and STING agonists have been receiving great attention for their development and clinical translation. Despite exciting results in preclinical work, the application of STING agonists to cancer therapy remains challenging due to their poor pharmacokinetic and physicochemical properties, as well as toxic side effects they produce. Here, we summarize the dichotomous role of cGAS-STING in cancer and discuss the limitations of cancer immunotherapy based on STING activation as well as feasible strategies to overcome them to achieve tumor regression.