title: Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.
abstract: 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.
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: M R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver.
authors.forename: K A
authors.initials: KA
authors.lastname: Schrader
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: E
authors.initials: E
authors.lastname: Pleasance
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: C
authors.initials: C
authors.lastname: Ch'ng
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: N
authors.initials: N
authors.lastname: Dar
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver.
authors.forename: S
authors.initials: S
authors.lastname: Yip
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, Vancouver.
authors.forename: D J
authors.initials: DJ
authors.lastname: Renouf
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: J E
authors.initials: JE
authors.lastname: Schein
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: A J
authors.initials: AJ
authors.lastname: Mungall
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: R
authors.initials: R
authors.lastname: Moore
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver.
authors.forename: B S
authors.initials: BS
authors.lastname: Sheffield
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver.
authors.forename: T
authors.initials: T
authors.lastname: Ng
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver Department of Medical Genetics, University of British Columbia, Vancouver Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, Canada.
authors.forename: S J M
authors.initials: SJ
authors.lastname: Jones
authors.affiliation: British Columbia Cancer Agency, Canada's Michael Smith Genome Sciences Centre, Vancouver Department of Medical Genetics, University of British Columbia, Vancouver.
authors.forename: M A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, Vancouver.
authors.forename: J
authors.initials: J
authors.lastname: Laskin
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, Vancouver hlim@bccancer.bc.ca.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lim
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D000809:Angiotensins / Q000037:antagonists & inhibitors / Q000235:genetics; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019295:Computational Biology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077405:Irbesartan; D009362:Neoplasm Metastasis; D057285:Precision Medicine; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*; D018808:Transcription Factor AP-1 / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
chemical_list: D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D001713:Biphenyl Compounds; D013777:Tetrazoles; D018808:Transcription Factor AP-1; D000077405:Irbesartan
keywords: AP-1 complex; RNA expression analysis; chemo-refractory colon cancer; irbesartan; mismatch repair defective; personalized medicine