Pharmacological Modulation of the STING Pathway for Cancer Immunotherapy

被引:97
作者
Berger, Gilles [1 ,2 ]
Marloye, Mickael [1 ]
Lawler, Sean E. [2 ]
机构
[1] Univ Libre Bruxelles, Fac Pharm, Microbiol Bioorgan & Macromol Chem, Blvd Triomphe, B-1050 Brussels, Belgium
[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Harvey Cushing Neurooncol Labs, Boston, MA 02115 USA
关键词
CYCLIC GMP-AMP; C-DI-GMP; VASCULAR-DISRUPTING AGENT; 5,6-DIMETHYLXANTHENONE-4-ACETIC ACID DMXAA; IMMUNE CHECKPOINT BLOCKADE; FLAVONE ACETIC-ACID; KAPPA-B ACTIVATION; I INTERFERON; ENDOGENOUS; 2ND-MESSENGER; TUMOR MICROENVIRONMENT;
D O I
10.1016/j.molmed.2019.02.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The advent of immunotherapy in recent years has shown the potential to revolutionize the treatment of cancer. Unleashing antitumor T cell responses via immune checkpoint blockade has led to remarkable responses in previously untreatable tumors. The master regulator of interferon-mediated antiviral responses-stimulator of interferon genes (STING)-has now emerged as a critical mediator of innate immune sensing of cancer, and is a promising target for local immunostimulation, promoting intratumoral inflammation, and facilitating antitumor T cell responses. Pharmacological activation of the STING pathway can lead to T cell-mediated tumor regression in preclinical tumor models, and novel STING activating small molecules are now being tested in clinical trials. Here we will introduce the STING pathway and review the current state of drug development.
引用
收藏
页码:412 / 427
页数:16
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