The fate and future of patents on human genes and genetic diagnostic methods.

Nat Rev Genet. 2012;13(6):441-8

Authors: Huys I, Matthijs G, Van Overwalle G

Abstract
Since the 1970s, patents on human genes and genetic diagnostic methods have been granted under the assumption that they stimulate the development of diagnostic methods and therapeutic products. However, the principles and practices of patenting vary between jurisdictions. Do patent holders, researchers, clinicians and patients really benefit from this heterogeneous patent system? We discuss the problems that result from the current system and suggest how they might be solved by altering the way in which patents are granted and/or licensed.

PMID: 22596320 [PubMed - in process]

Personalized Medicine: What Exactly Is It and Can We Truly Measure It?

J Clin Oncol. 2012 May 14;

Authors: Kelly CM, Pritchard KI

PMID: 22585700 [PubMed - as supplied by publisher]

Circumventing cancer drug resistance in the era of personalized medicine.

Cancer Discov. 2012 Mar;2(3):214-26

Authors: Garraway LA, Jänne PA

Abstract
All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance. Experimental approaches that can help predict the eventual clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, are rapidly identifying novel resistance mechanisms. In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies. We further discuss advantages and disadvantages of experimental strategies that can be used to identify drug resistance mechanism(s).

PMID: 22585993 [PubMed - in process]

Stumbling Blocks on the Path to Personalized Medicine in Breast Cancer: The Case of PARP Inhibitors for BRCA1/2-Associated Cancers.

Cancer Discov. 2011 Jun;1(1):29-34

Authors: Balmaña J, Domchek SM, Tutt A, Garber JE

Abstract
The popular vision for the future of oncology includes the rational design of therapies inhibiting specific targets, for which development would be less expensive and the chance of success greater because the agent, the target, and a population predicted to benefit maximally would be known from the outset. In the breast cancer arena, successful targeted therapies have entered clinical practice. Recently, patients with BRCA-associated cancers have been identified as eligible for novel investigational therapies targeting their genetic deficiency. Preclinical data, phase I results, and 2 phase II proof-of-concept studies support the continued development of PARP inhibitors, either as single agents or in combination with specific cytotoxic drugs in this setting. In this article, we provide a brief review of current developments concerning PARP inhibitors in BRCA-associated cancers and express concerns about challenges to further development.

PMID: 22586318 [PubMed - in process]

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]

SNP Web Resources and Their Potential Applications in Personalized Medicine.

Curr Drug Metab. 2012 May 16;

Authors: Wang J, Pang GS, Chong SS, Lee CG

Abstract
Single nucleotide polymorphisms (SNPs) are the commonest genetic variant in the human genome and have been associated with inter-individual differences in drug response. Finding the causative SNPs underlying variations in drug response has been a cornerstone of personalized medicine. However, as there are over 19 million SNPs, the task of finding causative SNPs underlying differences in drug response using in vitro and in vivo methods can be intimidating. SNP related web resources can be invaluable in the search for SNPs relevant to drug response phenotypes as they represent relatively cheaper yet efficient ways of prioritizing relevant SNPs for further study. These resources serve as repositories of SNP information or contain in silico tools that can predict the functionality of a SNP. More sophisticated resources integrate the information repository function with the predictive function to create a one stop SNP resource for researchers. SNP related web resources can also aid researchers in planning and analyzing different types of genetic association studies by aiding in selecting SNPs for genotyping in these studies. The focus of this mini review is to outline the SNP related web resources that are available to researchers and how these resources may aid researchers studying SNP-drug response phenotype associations. Through efficient utilization of SNP related web resources, researchers will hopefully be able accelerate the pace of SNP related research in pharmacogenomics by identifying high risk SNP variants contributing to drug response as well as developing novel therapeutic targets based on understanding how SNPs alter drug response pathways.

PMID: 22591348 [PubMed - as supplied by publisher]

Personalized medicine: Potential, barriers and contemporary issues.

Curr Drug Metab. 2012 May 16;

Authors: Sorich MJ, McKinnon RA

Abstract
Personalized medicine has gained significant attention over the last decade as technologies for understanding biological differences between individuals have advanced dramatically. There are many potential benefits of personalized medicine including minimizing risk of drug toxicity, increasing benefit from drugs used, contributing to the sustainability of the healthcare system and facilitating drug discovery and development programs. Unfortunately there are also many barriers such as cost, complexity, high quality evidence requirements, and the need for further education that have limited the clinical translation of pharmacogenomic tests to date. Issues that need to be clarified are also considered, such as the regulatory evidence requirements for pharmacogenomic tests and the need for multiple pathways and for pharmacogenomic marker development. These issues surrounding personalized medicine are contextualized using three contemporary examples of pharmacogenetic tests involving drug metabolising enzymes: UDP glucuronosyltransferase 1A1 and irinotecan toxicity, cytochrome P450 2C19 and clopidogrel efficacy, and cytochrome P450 2C9 and warfarin dosing.

PMID: 22591350 [PubMed - as supplied by publisher]

Editorial: SNPs of Drug Metabolic Enzymes and Personalized Medicine Part II.

Curr Drug Metab. 2012 May 16;

Authors: Wei DQ, Chen Q

Abstract
EDITORIAL.

PMID: 22591352 [PubMed - as supplied by publisher]

Personalized medicine and patient modelling in oncology.

Int J Comput Assist Radiol Surg. 2012 May 17;

Authors:

PMID: 22592241 [PubMed - as supplied by publisher]