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

被引：32

作者：

Jones, M. R. ^{[1
]}

Schrader, K. A. ^{[2
]}

Shen, Y. ^{[1
]}

Pleasance, E. ^{[1
]}

Ch'ng, C. ^{[1
]}

Dar, N. ^{[1
]}

Yip, S. ^{[3
]}

Renouf, D. J. ^{[4
]}

Schein, J. E. ^{[1
]}

Mungall, A. J. ^{[1
]}

Zhao, Y. ^{[1
]}

Moore, R. ^{[1
]}

Ma, Y. ^{[1
]}

Sheffield, B. S. ^{[3
]}

Ng, T. ^{[3
]}

Jones, S. J. M. ^{[1
,2
,5
]}

Marra, M. A. ^{[1
,2
]}

Laskin, J. ^{[4
]}

Lim, H. J. ^{[4
]}

机构：

[1] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada

[2] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[3] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC, Canada

[4] British Columbia Canc Agcy, Div Med Oncol, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada

[5] Simon Fraser Univ, Dept Mol Biol & Biochem, Vancouver, BC, Canada

来源：

ANNALS OF ONCOLOGY | 2016年 / 27卷 / 05期

关键词：

personalized medicine; AP-1; complex; irbesartan; chemo-refractory colon cancer; RNA expression analysis; mismatch repair defective; GROWTH-FACTOR-BETA; FAMILY-MEMBERS; COLON-CANCER; CELLS; JUN; EXPRESSION; THERAPY; INHIBITION; SURVIVAL; AP-1;

D O I：

10.1093/annonc/mdw060

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：801 / 806

页数：6

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