Many different defects in cancer can lead to genomic instability. These various different mechanisms include defects in DNA repair or chromosome segregation during mitosis, and lead to chromosomes or fragments of chromosomes ending up in the cytoplasmic.
PhD students Mengting Chen and Renske Linstra have reviewed how cytoplasmic DNA triggers inflammatory signaling, and describe that inflammatory signaling provides both tumor-suppressive as well as tumor-promoting traits.
To prevent clearance by the immune system, genomically instable cancer cells need to adapt to escape immune surveillance. The various different adaptive mechanisms by which tumor cells suppress inflammatory signaling or locally inhibit immune cells are discussed. Moreover, approaches are considered how these adaptive mechanisms can be therapeutically exploited to activate the immune system to eradicate genomically instable cancers. The review ‘Genomic instability, inflammatory signaling and response to cancer immunotherapy’ was published in: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.
Read more about this study: Genomic instability, inflammatory signaling and response to cancer immunotherapy
Cancers with mutations in BRCA1 or BRCA2 are particularly genomically instable. BRCA1 and BRCA2 are key regulators of DNA maintenance through homologous recombination (HR). Consequently, Mutations in BRCA1 and BRCA2 lead to defective repair of double-stranded DNA breaks (DSBs) and an inability to protect stalled replication forks. Of note, BRCA1/2 mutations cause hereditary breast and ovarian cancer.
In our previous work, we discovered that defective BRCA1/2 leads to cytoplasmic DNA and activation of the cGAS/STING pathway, which triggers inflammatory signaling. In a recent opinion article in Trends in Cancer, Eileen Parkes (Oxford University) and Marcel van Vugt review the current literature on how BRCA1/2 mutant cancer instigate inflammatory signaling, and how these cancers adapt to it. Finally, we discuss therapeutic consequences and opportunities to engage the immune system to target BRCA1/2 cancers.
Read more about this study: When breaks get hot: inflammatory signaling in BRCA1/2-mutant cancers
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