Personal Genome

HER2 Signaling and Resistance to the Anti-EGFR Monoclonal Antibody Cetuximab: A Further Step toward Personalized Medicine for Patients with Colorectal Cancer.

Cancer Discov. 2011 Nov;1(6):472-4

Authors: Ciardiello F, Normanno N

Abstract
Primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) drugs are clinically relevant problems in patients with metastatic colorectal carcinoma. A complex network of molecular alterations is involved in this phenomenon. Bertotti et al. report the development of serially transplantable groups of tumor xenografts in immune-deficient mice from patient-derived, genetically characterized metastatic colorectal carcinoma samples. These experimental models ("xenopatients") might represent a novel approach to discover and characterize the mechanisms of resistance to anti-EGFR therapy and other molecularly targeted therapies in metastatic colorectal carcinoma. In this respect, Bertotti et al. were able to identify HER2 gene amplification as one such mechanism of resistance to anti-EGFR therapy. Cancer Discovery; 1(6); 472-74. ©2011 AACR.

PMID: 22586650 [PubMed - in process]

Operational Implementation of Prospective Genotyping for Personalized Medicine: The Design of the Vanderbilt PREDICT Project.

Clin Pharmacol Ther. 2012 May 16;

Authors: Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH, Delaney JT, Bowton E, Brothers K, Johnson K, Crawford DC, Schildcrout J, Masys DR, Dilks HH, Wilke RA, Clayton EW, Shultz E, Laposata M, McPherson J, Jirjis JN, Roden DM

Abstract
The promise of "personalized medicine" guided by an understanding of each individual's genome has been fostered by increasingly powerful and economical methods to acquire clinically relevant information. We describe the operational implementation of prospective genotyping linked to an advanced clinical decision-support system to guide individualized health care in a large academic health center. This approach to personalized medicine entails engagement between patient and health-care provider, identification of relevant genetic variations for implementation, assay reliability, point-of-care decision support, and necessary institutional investments. In one year, approximately 3,000 patients, most of whom were scheduled for cardiac catheterization, were genotyped on a multiplexed platform that included genotyping for CYP2C19 variants that modulate response to the widely used antiplatelet drug clopidogrel. These data are deposited into the electronic medical record (EMR), and point-of-care decision support is deployed when clopidogrel is prescribed for those with variant genotypes. The establishment of programs such as this is a first step toward implementing and evaluating strategies for personalized medicine.

PMID: 22588608 [PubMed - as supplied by publisher]