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

• Published in: Annals of oncology Vol. 27; no. 5; pp. 801 - 806
• Main Authors: Jones, M.R., Schrader, K.A., Shen, Y., Pleasance, E., Ch'ng, C., Dar, N., Yip, S., Renouf, D.J., Schein, J.E., Mungall, A.J., Zhao, Y., Moore, R., Ma, Y., Sheffield, B.S., Ng, T., Jones, S.J.M., Marra, M.A., Laskin, J., Lim, H.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2016; Oxford University Press
• Subjects: Aged; Angiotensin Receptor Antagonists - administration & dosage; Angiotensins - antagonists & inhibitors; Angiotensins - genetics; AP-1 complex; Biphenyl Compounds - administration & dosage; chemo-refractory colon cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Computational Biology; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Irbesartan; mismatch repair defective; Neoplasm Metastasis; Original; personalized medicine; Precision Medicine; Renin-Angiotensin System - drug effects; RNA expression analysis; Tetrazoles - administration & dosage; Transcription Factor AP-1 - genetics; Transcriptome - genetics; chemo-refractory colon cancer; AP-1 complex; irbesartan; RNA expression analysis; mismatch repair defective; personalized medicine
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdw060

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.