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Proteome Science

, 4:5

First Online: 04 April 2006Received: 09 February 2006Accepted: 04 April 2006

Abstract

During the past decade, genomic microarrays have been applied with some success to the molecular profiling of breast tumours, which has resulted in a much more detailed classification scheme as well as in the identification of potential gene signature sets. These gene sets have been applied to both the prognosis and prediction of outcome to treatment and have performed better than the current clinical criteria. One of the main limitations of microarray analysis, however, is that frozen tumour samples are required for the assay. This imposes severe limitations on access to samples and precludes large scale validation studies from being conducted. Quantitative reverse transcriptase polymerase chain reaction qRT-PCR, on the other hand, can be used with degraded RNAs derived from formalin-fixed paraffin-embedded FFPE tumour samples, the most important and abundant source of clinical material available. More recently, the novel DASL cDNA-mediated Annealing, Selection, extension and Ligation assay has been developed as a high throughput gene expression profiling system specifically designed for use with FFPE tumour tissue samples.

However, we do not believe that genomics is adequate as a sole prognostic and predictive platform in breast cancer. The key proteins driving oncogenesis, for example, can undergo post-translational modifications; moreover, if we are ever to move individualization of therapy into the practical world of blood-based assays, serum proteomics becomes critical. Proteomic platforms, including tissue micro-arrays TMA and protein chip arrays, in conjunction with surface-enhanced laser desorption ionization time-of-flight mass spectrometry SELDI-TOF-MS, have been the technologies most widely applied to the characterization of tumours and serum from breast cancer patients, with still limited but encouraging results.

This review will focus on these genomic and proteomic platforms, with an emphasis placed on the utilization of FFPE tumour tissue samples and serum, as they have been applied to the study of breast cancer for the discovery of gene signatures and biomarkers for the early diagnosis, prognosis and prediction of treatment outcome. The ultimate goal is to be able to apply a systems biology approach to the information gleaned from the combination of these techniques in order to select the best treatment strategy, monitor its effectiveness and make changes as rapidly as possible where needed to achieve the optimal therapeutic results for the patient.

AbbreviationsAOadjuvant online

BCL2B-cell CLL-lymphoma 2

BRCA1-2breast cancer 1-2, early onset

CA IXcarbonic anhydrase IX

CD117v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

CDKcyclin D kinase

CK5-6cytokeratin 5-6

c-Mycv-myc myelocytomatosis viral oncogene homolog

Cox-2cyclooxygenase-2

DASLcDNA-mediated Annealing, Selection, extension and Ligation

DFSdisease-free survival

EGFRepidermal growth factor receptor 1

ERestrogen receptor

FFPEformalin-fixed paraffin-embedded

FISHfluorescence in situ hybridization

GHIGenomic Health Incorporated

HDAChistone deacetylase

HER2epidermal growth factor receptor 2

Ki67antigen identified by monoclonal antibody Ki-67

LNlymph node

MINDACTMicroarray for Node Negative Disease may Avoid Chemotherapy

MUCmucin

NSABPNational Surgical Adjuvant Breast and Bowel Project

NSAIDnon-steroidal anti-inflammatory drug

OSoverall survival

p16cyclin-dependent kinase inhibitor 2A

p21cyclin-dependent kinase inhibitor 1A

p27cyclin-dependent kinase inhibitor 1B

p53tumour suppressor protein p53

p63tumour protein p63

PGRprogesterone receptor

PTENphosphatase and tensin homolog

qRT-PCRquantitative reverse transcriptase polymerase chain reaction

RSrecurrence score

SELDI-TOF-MSsurface-enhanced laser-desorption ionization time-of-flight mass spectrometry

TMAtissue microarray

Electronic supplementary materialThe online version of this article doi:10.1186-1477-5956-4-5 contains supplementary material, which is available to authorized users.

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Author: Mark Abramovitz - Brian Leyland-Jones

Source: https://link.springer.com/







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