Multifaceted roles of cGAS-STING pathway in the lung cancer: from mechanisms to translation

PeerJ. 2024 Nov 22:12:e18559. doi: 10.7717/peerj.18559. eCollection 2024.

Abstract

Lung cancer (LC) remains one of the most prevalent and lethal malignancies globally, with a 5-year survival rate for advanced cases persistently below 10%. Despite the significant advancements in immunotherapy, a substantial proportion of patients with advanced LC fail to respond effectively to these treatments, highlighting an urgent need for novel immunotherapeutic targets. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has gained prominence as a potential target for improving LC immunotherapy due to its pivotal role in enhancing anti-tumor immune responses, augmenting tumor antigen presentation, and promoting T cell infiltration. However, emerging evidence also suggests that the cGAS-STING pathway may have pro-tumorigenic effects in the context of LC. This review aims to provide a comprehensive analysis of the cGAS-STING pathway, including its biological composition, activation mechanisms, and physiological functions, as well as its dual roles in LC and the current and emerging LC treatment strategies that target the pathway. By addressing these aspects, we intend to highlight the potential of the cGAS-STING pathway as a novel immunotherapeutic target, while also considering the challenges and future directions for its clinical application.

Keywords: Immunotherapy; Lung cancer; Molecular mechanism; STING; cGAS.

Publication types

  • Review

MeSH terms

  • Humans
  • Immunotherapy* / methods
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Membrane Proteins* / metabolism
  • Nucleotidyltransferases* / genetics
  • Nucleotidyltransferases* / immunology
  • Nucleotidyltransferases* / metabolism
  • Signal Transduction*

Substances

  • Nucleotidyltransferases
  • Membrane Proteins
  • cGAS protein, human
  • STING1 protein, human

Grants and funding

This work was supported by the National Key R&D Program of China (No. 2023YFF0720300), the Science and Technology Department of Sichuan Province (No. 2024YFFK0156), the Key Projects of Science and Technology Plan of Inner Mongolia Autonomous Region (No. 201802115), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No. ZYYCXTD-D-202209) and the Sichuan Provincial Administration of Traditional Chinese Medicine (2024MS170). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.