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PMID: 21643984 Published · ppublish English Journal Article Review

Somatic variation and cancer: therapies lost in the mix.

Human genetics ·Vol. 130 ·No. 1 ·2011-07-00 ·Pages 79-91

Biankin AV, Hudson TJ

Abstract

Cancer arises as a consequence of mutations in genomes of cancer cells, which over time allow them to proliferate and spread to distant sites. Large-scale sequencing of cancer genomes is revealing an increasing number of potential driver mutations that may allow specific targeting of cancer genes, proteins, and pathways. Comprehensive views of cancer genomes are also revealing enormous heterogeneity of mutation profiles, even among tumours derived from the same organs and having similar pathological characteristics. There are now many examples where mutation profiles observed in tumours have been shown to correlate with clinical features of disease, drug response, and patient outcomes. When ignored, molecular heterogeneity can lead to failures in drug development, as drugs that may have efficacy in subgroups of patients with specific molecular phenotypes may show marginal response when tested in large groups of unselected patients. This article explores issues relevant to the clinical translation of sequence-based mutation profiles in the clinical development of targeted therapies and in the future management of cancer patients.

MeSH Terms
Biomarkers, Tumor/analysis DNA Damage Genes, Neoplasm Genetic Variation Genotype Humans Molecular Targeted Therapy Mutation Neoplasms/genetics,therapy Randomized Controlled Trials as Topic/methods
Chemicals
Biomarkers, Tumor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Biankin Andrew V
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.
Hudson Thomas J
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Article Info
Journal
Human genetics
Abbr.
Hum Genet
ISSN
1432-1203
DOI
10.1007/s00439-011-1010-0
Published
2011-07-00
Epub
2011-00-05
Pages
79-91
Language
English
Region
Germany
NLM ID
7613873
Subset
IM
External Links
PubMed source DOI: 10.1007/s00439-011-1010-0 View journal details
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