Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence?

Çolakoğlu, Tamer; Yıldırım, Sedat; Kayaselçuk, Fazi̇let; Nursal, Tarık Zafer; Ezer, Ali; Noyan, Turgut; Karakayalı, H.; Haberal, Mehmet

doi:10.1016/j.amjsurg.2007.05.061

Cited by 94 publications

(96 citation statements)

References 43 publications

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“…c-MYC, cyclin D1 and CD44 have been reported as targets of the wnt/β-catenin pathway (He et al, 1998;Tetsu and McCormick, 1999). Frequent mutations of the β-catenin gene were found in chemically induced colon tumors in both rat and mouse carcinogenesis models (Dashwood et al, 1998;Takahashi et al, 1998;Suzui et al, 1999), suggesting that the APC-β-catenin pathway plays an important role in the development of colon carcinogenesis in rodents, as seen in humans. Recent reports shown that activation of Wnt/β-catenin signaling is important for both initiation and progression of cancers of different tissues/organs, including liver (Lee et al, 2006;Ashokkumar and Sudhandiran, 2011), thus, Wnt/β-catenin signaling pathway is becoming a promising target for chemoprevention and chemotherapy in CRC (Herbst and Kolligs, 2007;Luo et al, 2007;Ashokkumar and Sudhandiran, 2011).…”

Section: 2201 Potential Targets For Prevention Of Colorectal Cancer:mentioning

confidence: 99%

“…Published reports suggested that the association of phosphoinositide-3-kinase (PI3K)/Akt pathway, in colon tumorigenesis (Engelman, 2009;Palozza et al, 2009). Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human CRC (Colakoglu et al, 2008). Both catalytic (p110) and regulatory (p85) subunits of PI3K initiates a signal transduction cascade that promotes cancer cell growth, survival and metabolism (Rychahou et al, 2005;Engelman, 2009) which further keenly involved in protecting the cells from undergoing apoptotic mode of cell death (Jung et al, 2000;Lee et al, 2010) (Figure 2).…”

Section: Pi3k/akt/mtor Pathway As a Targetmentioning

confidence: 99%

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Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

Pandurangan¹

2013

Asian Pacific Journal of Cancer Prevention

172

146

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Colorectal cancer (CRC) is one of the most common cancers in many parts of the world. Its development is a multi-step process involving three distinct stages, initiation that alters the molecular message of a normal cell, followed by promotion and progression that ultimately generates a phenotypically altered transformed malignant cell. Reports have suggested an association of the phosphoinositide-3-kinase (PI3K)/Akt pathway with colon tumorigenesis. Activation of Akt signaling and impaired expression of phosphatase and tensin homolog (PTEN) (a negative regulator of Akt) has been reported in 60-70% of human colon cancers and inhibitors of PI3K/Akt signaling have been suggested as potential therapeutic agents. Around 80% of human colon tumors possess mutations in the APC gene and half of the remainder feature β-catenin gene mutations which affect downstream signaling of the PI3K/Akt pathway. In recent years, there has been a great focus in targeting these signaling pathways, with natural and synthetic drugs reducing the tumor burden in different experiment models. In this review we survey the role of PI3K/Akt/mTOR and Wnt signaling in CRC.

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Section: 2201 Potential Targets For Prevention Of Colorectal Cancer:mentioning

confidence: 99%

Section: Pi3k/akt/mtor Pathway As a Targetmentioning

confidence: 99%

Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

Pandurangan¹

2013

Asian Pacific Journal of Cancer Prevention

172

146

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“…[91][92][93] Regarding response to EGFR-targeted therapies, several studies have shown an association with PTEN loss and lack of response to cetuximab and panitumumab. [94][95][96][97] However, other published studies failed to demonstrate a clear correlation between loss of PTEN expression and response to anti-EGFR therapy.…”

mentioning

confidence: 99%

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

Sepulveda

Hamilton²,

Allegra

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

124

101

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Objectives.-To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens.Methods.-The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted.Results.-Twenty-one guideline statements were established.Conclusions.-Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

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“…PTEN expression showed a negative correlation with young age, female sex, and left-sided (distal) tumors. On multivariate analysis, low PTEN expression (PTEN loss) was noted as an independent parameter for local recurrence (P=0.024) in their study (Colakoglu et al, 2008). We analysed PTEN as prognostic and predictive biomarker in m CRC.…”

Section: Discussionmentioning

confidence: 99%

“…We found in the rate of 35% PTEN loss in m CRC. Colakoglu et al (2008) have reported PTEN expression and its correlation with the prognostic factors in CRC. PTEN expression showed a negative correlation with young age, female sex, and left-sided (distal) tumors.…”

Section: Discussionmentioning

confidence: 99%

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

Kara

Duman²,

Kara³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

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Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence?

Cited by 94 publications

References 43 publications

Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

Potential Targets for Prevention of Colorectal Cancer: a Focus on PI3K/Akt/mTOR and Wnt Pathways

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy

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