Targeting the stimulator of interferon genes (STING) in breast cancer

Abstract

Breast cancer has a high occurrence rate globally and its treatment has demonstrated clinical efficacy with the use of systemic chemotherapy and immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration and the accumulation of immunosuppressive cells within tumours are the primary factors responsible for the inadequate clinical effectiveness of breast cancer treatment. The stimulator of interferon genes (STING) represents a pivotal protein in the innate immune response. Upon activation, STING triggers the activation and enhancement of innate and adaptive immune functions, resulting in therapeutic benefits for malignant tumours. The STING signalling pathway in breast cancer is influenced by various factors such as deoxyribonucleic acid damage response, tumour immune microenvironment, and mitochondrial function. The use of STING agonists is gaining momentum in breast cancer research. This review provides a comprehensive overview of the cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, its agonists, and the latest findings related to their application in breast cancer.

Epithelial-Mesenchymal Transition in Tumor Cells and Activated Intra-Tumor Immunity Respectively Are Correlated With Prognosis and Chemo-Sensitivity in Breast Cancer Patients With a Non-pathological Response to Neoadjuvant Chemotherapy

“…However, this small-scaled exploratory study has indicated that activated intra-tumor immune microenvironments may play an important role in pathological responses to NAC, and that the up-regulation of vimentin and v+ in the residual tumors may be pivotal prognostic factors in non-pCR cases to NAC. Enhancement of intra-tumor immunity before the NAC introduction using pre-operative radiotherapy or immunepotentiating agents might provide a greater anti-tumor activity of NAC [27][28][29]. Additionally, anti-EMT agents together with NAC might improve the outcome of patients with TNBCs [30,31].…”

Genomic Features of Homologous Recombination Deficiency in Breast Cancer: Impact on Testing and Immunotherapy

“…Both innate and adaptive immune cells play a role in these antithetical responses. Altered DNA damage responses (DDRs) following constitutional mutations of the genes involved in the HRR pathway or exposure to cytotoxic agents cause activation of the inflammatory STING (stimulating interferon gene) pathway leading to anti-tumor response (Figure 4) [90]. The soluble DNA released from defective DDR will cause an enzymatic activation of cyclic guanosine monophosphate-adenosine monophosphate synthetase (cGAS) leading to the synthesis of the second messenger, 2 ′ 3 ′ -Cyclic GMP-AMP (cGAMP) [91].…”