As part of a personalized oncogenomics initiative whole genome and transcriptome sequencing was used to interrogate a mismatch repair-deficient tumour from a patient suffering from metastatic colorectal cancer resistant to standard chemotherapy and radiation. Analysis of gene expression outliers identified high expression of the activating protein-1 (AP-1) transcriptional complex, indicating potential oncogene addiction. Based on this analysis, the possibility of treatment targeting the renin–angiotensin system upstream of the AP-1 complex was raised and a trial of the angiotensin receptor blocker irbesartan was initiated. The patient's disease exhibited a profound and durable response to this treatment indicating a new potential therapeutic axis for patients with similar genomic indications.
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