Core Viewpoint - The cGAS-STING pathway plays a crucial role in detecting tumor-derived DNA, influencing both spontaneous and treatment-induced responses, and establishing a delicate balance between pathological inflammation and protective immune responses [2][3]. Group 1: Overview of cGAS-STING Pathway - The review published in Nature Reviews Cancer discusses the dual roles of the cGAS-STING pathway in cancer, highlighting both its pro-cancer and anti-cancer effects [5]. - It provides a comprehensive analysis of the diverse sources of cGAS-STING activating ligands and their prevalence in various human cancers, including DNA abnormalities caused by chromosomal instability, replication stress, telomere shortening, and treatment-induced DNA damage [7][8]. Group 2: Dual Role in Tumor Progression - The review emphasizes the different outcomes mediated by cGAS-STING activation at various stages of tumor initiation, progression, and metastasis, noting its critical anti-tumor role during tumor initiation and potential pro-tumor effects during tumor progression [8][12]. Group 3: Clinical Implications and Challenges - The review systematically reviews clinical trial results of STING agonists, such as ADU-S100 and MK-1454, and analyzes the limited efficacy due to factors like short drug half-life and differences in tumor microenvironments between humans and mice [14]. - It details the multi-layered negative regulatory networks that limit the anti-tumor effects of the cGAS-STING pathway, including DNA uptake barriers and differential responses of innate and adaptive immune cells [14]. Group 4: Future Directions - The review proposes several optimization strategies for enhancing the efficacy of cGAS-STING-targeted therapies, such as selective induction of mitochondrial DNA release and the development of drug delivery systems that enable spatiotemporal control of activation [15]. - It also suggests that transient inhibition of cGAS-STING signaling may normalize immune responses and enhance the effectiveness of immunotherapy, referencing recent successful cases in early clinical trials [16][17].

Group 1 - The Nobel Prize announcement dates for 2025 are set for October 6, 7, and 8, covering the Nobel Prizes in Physiology or Medicine, Physics, and Chemistry [2] - Chinese scientist Chen Zhijian has received multiple prestigious awards, including the Citation Laureate Award, and is considered the closest Chinese scientist to winning a Nobel Prize [2] - Chen Zhijian is recognized for his discovery of how nucleic acids trigger innate immune responses and autoimmune reactions within cells [3] Group 2 - Chen Zhijian was born in 1966 in Fujian Province, China, and graduated with a Bachelor's degree in Biology from Fujian Normal University in 1985 [5] - He obtained his Ph.D. in Biochemistry from the State University of New York at Buffalo in 1991, focusing on the ubiquitin pathway [5] - After his postdoctoral research at the Salk Institute, he worked in various biotech companies, contributing to cancer treatment drug development [5][6] Group 3 - In 1996, Chen collaborated with Harvard's Tom Maniatis to discover that kinases must be "activated" by ubiquitin for the NF-κB signaling pathway to function properly [6] - He established his laboratory at the University of Texas Southwestern Medical Center in 1997, focusing on the role of ubiquitin in immune responses [6] - His research led to significant findings regarding the immune response to RNA viruses and the discovery of key proteins involved in innate immunity [6][8] Group 4 - Chen Zhijian has received numerous awards, including the National Academy of Sciences Molecular Biology Award in 2012 and election to the National Academy of Sciences in 2014 [8] - He was awarded the Breakthrough Prize in Life Sciences in 2019 for elucidating the role of the DNA sensor cGAS in immune responses [11] - In 2023, he received the Horwitz Prize for discovering the cGAS-STING pathway, which is considered a leading indicator for future Nobel Prize winners [12] Group 5 - Chen was awarded the Lasker Basic Medical Research Award in 2024 for his work on the cGAS enzyme and its role in immune and inflammatory responses [15] - The Citation Laureate Award was given to him in 2025 for clarifying the fundamental mechanisms of the cGAS-STING pathway in innate immunity [19] - The awards he has received are indicative of a strong likelihood of future recognition with a Nobel Prize, as many past recipients of these awards have gone on to win the Nobel Prize [12][19]