Genomics|Update|Current: Genomics in the Scientific Literature - Personalized Medicine

Genomics in the Scientific Literature
Topics in the Scientific Literature


Personalized Medicine
1. Future of Personalized Medicine in Oncology: A Systems Biology Approach
Gonzalez-Angulo AM, et al.
J Clin Oncol 2010 Apr

J Clin Oncol. 2010 Apr 20. [Epub ahead of print]

Future of Personalized Medicine in Oncology: A Systems Biology Approach.
Gonzalez-Angulo AM, Hennessy BT, Mills GB.

The University of Texas M. D. Anderson Cancer Center, Houston, TX.

Abstract
The development of cost-effective technologies able to comprehensively assess DNA, RNA, protein, and metabolites in patient tumors has fueled efforts to tailor medical care. Indeed validated molecular tests assessing tumor tissue or patient germline DNA already drive therapeutic decision making. However, many theoretical and regulatory challenges must still be overcome before fully realizing the promise of personalized molecular medicine. The masses of data generated by high-throughput technologies are challenging to manage, visualize, and convert to the knowledge required to improve patient outcomes. Systems biology integrates engineering, physics, and mathematical approaches with biologic and medical insights in an iterative process to visualize the interconnected events within a cell that determine how inputs from the environment and the network rewiring that occurs due to the genomic aberrations acquired by patient tumors determines cellular behavior and patient outcomes. A cross-disciplinary systems biology effort will be necessary to convert the information contained in multidimensional data sets into useful biomarkers that can classify patient tumors by prognosis and response to therapeutic modalities and to identify the drivers of tumor behavior that are optimal targets for therapy. An understanding of the effects of targeted therapeutics on signaling networks and homeostatic regulatory loops will be necessary to prevent inadvertent effects as well as to develop rational combinatorial therapies. Systems biology approaches identifying molecular drivers and biomarkers will lead to the implementation of smaller, shorter, cheaper, and individualized clinical trials that will increase the success rate and hasten the implementation of effective therapies into the clinical armamentarium.

PMID: 20406928 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20406928?dopt=Abstract


2. Refocusing the war on cancer: the critical role of personalized treatment
Potti A, et al.
Sci Transl Med 2010 Apr;2(28):28cm13

Sci Transl Med. 2010 Apr 21;2(28):28cm13.

Refocusing the war on cancer: the critical role of personalized treatment.
Potti A, Schilsky RL, Nevins JR.

Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27708, USA.

Abstract
Despite very substantial investment and effort over the past 30 years, the overall survival rate of cancer patients has changed little. We propose that without a truly robust mechanism for selecting the right treatment for the right patient at the right time-the central concepts of personalized medicine-we will continue to see only incremental improvements and have little hope for substantial survival gains. We suggest that it is now imperative that future clinical trials be designed with a plan to incorporate biomarker development.

PMID: 20410527 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20410527?dopt=Abstract


3-. Using genetics and genomics strategies to personalize therapy for cancer: focus on melanoma
Nathanson KL
Biochem Pharmacol 2010 Apr

Biochem Pharmacol. 2010 Apr 20. [Epub ahead of print]

Using genetics and genomics strategies to personalize therapy for cancer: Focus on melanoma.
Nathanson KL.

351 BRB 2/3, University of Pennsylvania School of Medicine, 421 Curie Blvd, Philadelphia, PA 19104, United States.

Abstract
Individualizing therapeutic selection for patients is a major goal in cancer treatment today. This goal is best facilitated by understanding both an individual's inherited genetic variation and the somatic genetic changes arising during cancer development. Clinical decision making based on inherited genetic variation is done for those patients with cancer susceptibility syndromes and more generally to personalize drug dosing. Personalized medicine based on genetic and genomic changes within tumors is being applied more widely, with increased use of therapies targeted to somatic mutations and amplifications. Somatic mutations associated with resistance also are being used to select against therapies. Somatic point mutation testing being used clinically includes direct sequencing, short sequencing and single nucleotide interrogation. Single amplifications are commonly assessed using FISH or CISH; high throughput assessment of amplifications and deletions is done mainly on a research basis. Melanomas contain complex mutational profiles that allow them to be sub-grouped by their genetic and genomic profile, each of which then can be evaluated pre-clinically to determine their response to targeted therapies. BRAF V600E mutations are the most commonly found in melanoma; specific inhibitors of mutant BRAF have been developed and are currently in clinical trials. In addition, other melanoma sub-groups have been identified genetically, which respond to other inhibitors. These studies focus on somatic genetic changes in cancer, which can be targeted directly by therapies. However in the future, personalized medicine will use a combination of inherited and somatic genetics to select the optimal tailored therapy for each patient. Copyright © 2010. Published by Elsevier Inc.

PMID: 20412787 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20412787?dopt=Abstract