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Cancer as a system failure.

Wigle D, Jurisica I - Cancer Inform (2007)

View Article: PubMed Central - PubMed

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Subsequently, EGFR mutations have been investigated in several series of NSCLC tumors from surgically resected patients or in patients treated with gefitinib or erlotinib... One of the startling aspects of the Paez et al. paper was that despite sequencing of the exons encoding the activation loops of 47 of the 58 human receptor tyrosine kinase genes in the human genome in 58 NSCLC samples, only 3 of the tumors, all lung adenocarcinomas, showed heterozygous missense mutations in EGFR not present in the DNA from normal lung tissue from the same patients... Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%)... A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1... Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors... The authors concluded that patients with completely resected NSCLC and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors did not... This included the ERCC1 and the phosphatase and tensin homologue (PTEN)... The results were compared with the clinical outcomes in 187 patients with early-stage NSCLC who had received only surgical treatment... Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1... The authors concluded that both RRM1 and ERCC1 are determinants of survival after surgical treatment of early stage NSCLC... The paradox highlighted by these two papers is the possibility that the immunohistochemical presence of ERCC1 in conjunction with RRM1 may actually be beneficial in early stage NSCLC; however, this may not translate into benefit from receiving platinum-based adjuvant chemotherapy... Comprehensive analyses of interaction networks has suggested that links between hub proteins are systematically suppressed... Such networks would be theoretically more robust by reducing the likelihood of cross-talk between functional modules, which in turn would localize effects of deleterious perturbations... Interestingly, contrary to these earlier results, the “oncohubs” are highly interconnected, suggesting significant cross-talk between associated pathways.

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EGFR signaling pathway (Oda, Matsuoka et al. 2005) from EMBL-EBI Systems Biology Markup Language curated model repository ((Le Novere, Bornstein et al. 2006); http://www.ebi.ac.uk/compneur-srv/biomodels-main/publ-models.do?cmd=MODELS:SRT&sof=nam&sod=asc#models), visualized using CellDesigner 3.5.1 (http://www.systems-biology.org/cd/).
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f2-cin-05-10: EGFR signaling pathway (Oda, Matsuoka et al. 2005) from EMBL-EBI Systems Biology Markup Language curated model repository ((Le Novere, Bornstein et al. 2006); http://www.ebi.ac.uk/compneur-srv/biomodels-main/publ-models.do?cmd=MODELS:SRT&sof=nam&sod=asc#models), visualized using CellDesigner 3.5.1 (http://www.systems-biology.org/cd/).

Mentions: The protein-protein interaction network surrounding EGFR—RAS signaling contains a number of well-characterized proteins, as shown on an example from the EBI SMBL Model Repository (Oda, Matsuoka et al. 2005; Le Novere, Bornstein et al. 2006) in Figure 2, and visualized in CellDesigner 3.5.1 (http://www.systems-biology.org/cd/). Information from protein-protein interaction databases, such as OPHID/I2D ((Brown and Jurisica, 2005); http://ophid.utoronto.ca/i2d), further extends the potential to study and model these pathways under specific stimuli or in different tissues. Figure 3 shows one such visualization in NAViGaTor 1.1 (http://ophid.utoronto.ca/navigator), highlighting only core proteins, and suppressing other details by using alpha-blending. Individual nodes in the graph represent proteins, while edges correspond to known and predicted interactions. The color of individual nodes (except for red-highlighted ones) denotes different GeneOntology biological functions.


Cancer as a system failure.

Wigle D, Jurisica I - Cancer Inform (2007)

EGFR signaling pathway (Oda, Matsuoka et al. 2005) from EMBL-EBI Systems Biology Markup Language curated model repository ((Le Novere, Bornstein et al. 2006); http://www.ebi.ac.uk/compneur-srv/biomodels-main/publ-models.do?cmd=MODELS:SRT&sof=nam&sod=asc#models), visualized using CellDesigner 3.5.1 (http://www.systems-biology.org/cd/).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2666950&req=5

f2-cin-05-10: EGFR signaling pathway (Oda, Matsuoka et al. 2005) from EMBL-EBI Systems Biology Markup Language curated model repository ((Le Novere, Bornstein et al. 2006); http://www.ebi.ac.uk/compneur-srv/biomodels-main/publ-models.do?cmd=MODELS:SRT&sof=nam&sod=asc#models), visualized using CellDesigner 3.5.1 (http://www.systems-biology.org/cd/).
Mentions: The protein-protein interaction network surrounding EGFR—RAS signaling contains a number of well-characterized proteins, as shown on an example from the EBI SMBL Model Repository (Oda, Matsuoka et al. 2005; Le Novere, Bornstein et al. 2006) in Figure 2, and visualized in CellDesigner 3.5.1 (http://www.systems-biology.org/cd/). Information from protein-protein interaction databases, such as OPHID/I2D ((Brown and Jurisica, 2005); http://ophid.utoronto.ca/i2d), further extends the potential to study and model these pathways under specific stimuli or in different tissues. Figure 3 shows one such visualization in NAViGaTor 1.1 (http://ophid.utoronto.ca/navigator), highlighting only core proteins, and suppressing other details by using alpha-blending. Individual nodes in the graph represent proteins, while edges correspond to known and predicted interactions. The color of individual nodes (except for red-highlighted ones) denotes different GeneOntology biological functions.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Subsequently, EGFR mutations have been investigated in several series of NSCLC tumors from surgically resected patients or in patients treated with gefitinib or erlotinib... One of the startling aspects of the Paez et al. paper was that despite sequencing of the exons encoding the activation loops of 47 of the 58 human receptor tyrosine kinase genes in the human genome in 58 NSCLC samples, only 3 of the tumors, all lung adenocarcinomas, showed heterozygous missense mutations in EGFR not present in the DNA from normal lung tissue from the same patients... Among 761 tumors, ERCC1 expression was positive in 335 (44%) and negative in 426 (56%)... A benefit from cisplatin-based adjuvant chemotherapy was associated with the absence of ERCC1... Among patients who did not receive adjuvant chemotherapy, those with ERCC1-positive tumors survived longer than those with ERCC1-negative tumors... The authors concluded that patients with completely resected NSCLC and ERCC1-negative tumors appear to benefit from adjuvant cisplatin-based chemotherapy, whereas patients with ERCC1-positive tumors did not... This included the ERCC1 and the phosphatase and tensin homologue (PTEN)... The results were compared with the clinical outcomes in 187 patients with early-stage NSCLC who had received only surgical treatment... Among these 187 patients, the survival advantage was limited to the 30% of patients with tumors that had a high expression of both RRM1 and ERCC1... The authors concluded that both RRM1 and ERCC1 are determinants of survival after surgical treatment of early stage NSCLC... The paradox highlighted by these two papers is the possibility that the immunohistochemical presence of ERCC1 in conjunction with RRM1 may actually be beneficial in early stage NSCLC; however, this may not translate into benefit from receiving platinum-based adjuvant chemotherapy... Comprehensive analyses of interaction networks has suggested that links between hub proteins are systematically suppressed... Such networks would be theoretically more robust by reducing the likelihood of cross-talk between functional modules, which in turn would localize effects of deleterious perturbations... Interestingly, contrary to these earlier results, the “oncohubs” are highly interconnected, suggesting significant cross-talk between associated pathways.

No MeSH data available.