The genomic medicine frontier in human solid tumors: prospects and challenges
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Dienstmann, Rodrigo, Rodon, Jordi, Barretina, Jordi and Tabernero, Josep (2013) The genomic medicine frontier in human solid tumors: prospects and challenges. Journal of Clinical Oncology, 31 (15). pp. 1874-1884. ISSN 0732-183X
Abstract
Recent discoveries of genomic alterations underlying and promoting the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many
opportunities to conduct hypothesis-driven clinical trials. The ability to profile each cancer patient for actionable aberrations in a cost-effective way using high-throughput technologies
provides unprecedented opportunities for utilizing matched therapies in a selected patient population. The major challenges are to integrate and make biological sense of the
substantial genomic data derived from multiple platforms. Two different approaches for the analysis, interpretation and clinical applicability of genomic data are defined: (a) the
genomically-stratified model originates from the “one test - one drug” paradigm and is currently being expanded with an upfront multicategorical approach following advances in
multiplexed genotyping platforms; and (b) the comprehensive assessment model is based on whole genome/exome and transcriptome data and allows identification of novel drivers and subsequent therapies in the experimental setting. Tumor heterogeneity and evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will need to be addressed in the new scenario of early drug development. Logistical issues related to prescreening strategies and trial allocation, in
addition to concerns in the economic and ethical domains must be taken into consideration.
Here we present an historical view of how increased understanding of cancer genomics has been translated to the clinic and discuss the prospects and challenges for further
implementation of a personalized treatment strategy for human solid tumors.
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/8081 |