Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer

Personalised oncogenomics analysis revealed potential oncogene addiction of the AP-1 transcriptional complex in a chemo-refractory and MMR-deficient tumor from a patient with metastatic colon cancer. Based on this, treatment with the angiotensin receptor agonist irbesartan was initiated to target the renin-angiotensin system upstream of the AP-1 complex, leading to a profound and durable response.A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.