Tissue Microarray Analysis of EGFR Gene Amplification and Gain in Bulgarian Patients with Colorectal Cancer

Petrova, Diana; Jankova, Renata; Yosifova, Aleksandra; Tzenova, Vasselina; Dimova, Ivanka; Toncheva, Draga

doi:10.1159/000092646

Cited by 3 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…22). EGFR amplification, however, is a rare event in colon cancer, occurring at a frequency of <1% of cases (37)(38)(39). Consistent with this finding, examination of EGFR amplification status in cetuximab-sensitive and cetuximab-resistant cell lines in the present study failed to identify any lines with EGFR amplification.…”

Section: Discussionsupporting

confidence: 83%

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

et al. 2008

View full text Add to dashboard Cite

Cetuximab is a monoclonal antibody that targets the human epidermal growth factor receptor (EGFR). Although approved for use in EGFR-overexpressing advanced colorectal cancer, recent studies have shown a lack of association between EGFR overexpression and cetuximab response, requiring the identification of novel biomarkers predictive of response to this agent. To do so, 22 colon cancer cell lines were screened for cetuximab response in vitro and sensitive and resistant lines were identified. In sensitive cell lines, cetuximab induced a G 0 -G 1 arrest without inducing apoptosis. Notably, cetuximabsensitive but not cetuximab-resistant cell lines were preferentially responsive to EGF-stimulated growth. Whereas neither EGFR protein/mRNA expression nor gene copy number correlated with cetuximab response, examination of the mutation status of signaling components downstream of EGFR showed that cell lines with activating PIK3CA mutations or loss of PTEN expression (PTEN null) were more resistant to cetuximab than PIK3CA wild type (WT)/PTENexpressing cell lines (14 F 5.0% versus 38.5 F 6.4% growth inhibition, mean F SE; P = 0.008). Consistently, PIK3CA mutant isogenic HCT116 cells showed increased resistance to cetuximab compared with PIK3CA WT controls. Furthermore, cell lines that were PIK3CA mutant/PTEN null and Ras/BRAF mutant were highly resistant to cetuximab compared with those without dual mutations/PTEN loss (10.8 F 4.3% versus 38.8 F 5.9% growth inhibition, respectively; P = 0.002), indicating that constitutive and simultaneous activation of the Ras and PIK3CA pathways confers maximal resistance to this agent. A priori screening of colon tumors for PTEN expression status and PIK3CA and Ras/BRAF mutation status could help stratify patients likely to benefit from this therapy.

show abstract

Section: Discussionsupporting

confidence: 83%

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In addition to EGFR expression, a link between EGFR amplification and response to anti-EGFR monoclonal antibody-based treatment has been shown 19,25 . EGFR amplification, however, is known as a rare event in CRC, occurring at a frequency of less than 1% of cases 19,[26][27][28] . Therefore, this possibility was not considered in this study.…”

Section: Discussionmentioning

confidence: 99%

Combination Effect of Cetuximab with Radiation in Colorectal Cancer Cells

Shin

Kim

Lee

et al. 2010

Tumori

View full text Add to dashboard Cite

show abstract

Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer

Adams¹,

Maughan²

2007

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

The discovery over 20 years ago by the Nobel Laureate Stanley Cohen of epidermal growth factor and its receptor, followed by the recognition that this receptor is overexpressed in multiple cancer types, has been of phenomenal significance. From these events the 'Holy Grail' of targeted therapy has looked increasingly realistic. Over the last 5 years this work has come of age with the licensing of multiple agents targeting this important mitogenic pathway in multiple tumor types. However, these agents and the technology behind them, while impressive, have resulted in lower clinical response rates than anticipated. In this review we will focus on the epidermal growth factor receptor-targeted therapies in colorectal cancer, why our expectations from these therapies have not yet been fulfilled and how we may predict those cancers that are likely to respond or be resistant to these therapies through a greater appreciation of the intricacy, diversity and dynamism of cellular signaling mechanisms.

show abstract

Tissue Microarray Analysis of EGFR Gene Amplification and Gain in Bulgarian Patients with Colorectal Cancer

Cited by 3 publications

References 22 publications

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab

Combination Effect of Cetuximab with Radiation in Colorectal Cancer Cells

Predicting response to epidermal growth factor receptor-targeted therapy in colorectal cancer

Contact Info

Product

Resources

About