Targeting DNA damage response pathways to activate the STING innate immune signaling pathway in human cancer cells

Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer

Background Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. Methods We used i...

Integration of the DNA Damage Response with Innate Immune Pathways

The Role of chk2 in Response to DNA Damage in Cancer Cells

Accumulation of gene changes and chromosomal instability in response to cellular DNA damage lead to cancer. DNA damage induces cell cycle checkpoints pathways. Checkpoints regulate DNA replication and cell cycle progression, chromatin restructuring, and apoptosis. Checkpoint kinase 2 (chk2) is activated in response to DNA lesions. ATM phosphorylate chk2. The activated Chk2 kinase can phosphoryl...

Signaling pathways involved in chronic myeloid leukemia pathogenesis: the importance of targeting Musashi2-Numb signaling to eradicate leukemia stem cells

Objective(s): Chronic myeloid leukemia (CML) is a myeloid clonal proliferation disease defining by the presence of the Philadelphia chromosome that shows the movement of BCR-ABL1. In this study, the critical role of the Musashi2-Numb axis in determining cell fate and relationship of the axis to important signaling pathways such as Hedgehog and Notch that are essential ...

Molecular Pathways Targeting Hypoxic Cells through the DNA Damage Response

Exposure to hypoxia-induced replication arrest initiates a DNA damage response that includes both ATRand ATM-mediated signaling. DNA fiber analysis was used to show that these conditions lead to a replication arrest during both the initiation and elongation phases, and that this correlated with decreased levels of nucleotides. The DNA damage response induced by hypoxia is distinct from the clas...