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

Ann Oncol. 2016 May;27(5):801-6. doi: 10.1093/annonc/mdw060. Epub 2016 Feb 18.

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusions: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.

Keywords: AP-1 complex; RNA expression analysis; chemo-refractory colon cancer; irbesartan; mismatch repair defective; personalized medicine.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / administration & dosage
  • Angiotensins / antagonists & inhibitors
  • Angiotensins / genetics
  • Biphenyl Compounds / administration & dosage*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Computational Biology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Irbesartan
  • Neoplasm Metastasis
  • Precision Medicine*
  • Renin-Angiotensin System / drug effects
  • Tetrazoles / administration & dosage*
  • Transcription Factor AP-1 / genetics*
  • Transcriptome / genetics

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensins
  • Biphenyl Compounds
  • Tetrazoles
  • Transcription Factor AP-1
  • Irbesartan