Potential value of PTEN in predicting cetuximab response in colorectal cancer: An exploratory study

Razis, Evangelia; Briasoulis, Evangelos; Vrettou, Eleni; Skarlos, Dimosthenis; Papamichael, D.; Kostopoulos, Ioannis; Samantas, Epaminontas; Xanthakis, Ioannis; Bobos, Mattheos; Galanidi, Eleni; Bai, Maria; Gikonti, Ioanna; Koukouma, Alona; Kafiri, Georgia; Papakostas, Pavlos; Kalogeras, Konstantine T.; Kosmidis, P.; Fountzilas, George

doi:10.1186/1471-2407-8-234

Cited by 86 publications

(62 citation statements)

References 22 publications

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“…This latter study underlines the implication of the PI3K/AKT pathway in the modulation of response to cetuximab as it was also recently suggested in a small series of colorectal cancers in which the activation of this pathway by means of PI3KCA mutation and/or PTEN allelic loss was observed in 28% of the cases, all being nonresponders to cetuximab (75). It is probable that a global activation of the PI3K/AKT pathway is more relevant than PTEN inactivation to predict response to anti-EGFR antibodies because discrepant results have been reported on the predictive value of PTEN loss of expression (77,78), partly due to the use of immunohistochemistry, which is not yet standardized. Furthermore, we have suggested that the measurement of the phosphorylation of p70S6 kinase, which is a terminal effector of this pathway, could be a good predictor of response to cetuximab in colorectal cancer (79).…”

Section: Pi3k/akt Pathwaymentioning

confidence: 66%

Mutations and Response to Epidermal Growth Factor Receptor Inhibitors

Laurent‐Puig

Lièvre

Blons

2009

Clinical Cancer Research

114

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Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for a subgroup of patients with colorectal, lung, head and neck, and pancreatic cancers. In these tumors, the EGFR activation turns on at least five different signaling pathways (RAS/mitogen-activated protein kinase, phospholipase C, phosphatidylinositol 3-kinase/AKT, signal transducer and activator of transcription, and SRC/FAK pathways), which are intimately interconnected, and frequent mutations involving either the receptor itself or downstream effectors have been found. Up to now, it seems that alterations at the EGFR level has major importance in EGFR tyrosine kinase inhibitor response, whereas modifications of downstream effectors could lead to treatment resistance. Furthermore, our understanding of the mechanism of the EGFR network activation provides new hypotheses on potential new anticancer drugs that may be effective.

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Section: Pi3k/akt Pathwaymentioning

confidence: 66%

Mutations and Response to Epidermal Growth Factor Receptor Inhibitors

Laurent‐Puig

Lièvre

Blons

2009

Clinical Cancer Research

114

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“…Scoring was performed according to the relative semi-quantification method described originally by Perren [13] and widely used in many recent studies [14,15]. Representative areas of tumor were selected and scored un-DARIUSZ WANICZEK, MIROSLAW SNIETURA, JOANNA MLYNARCZYK-LISZKA, ET AL.…”

Section: Immunohistochemistrymentioning

confidence: 99%

PTEN expression profiles in colorectal adenocarcinoma and its precancerous lesions

Waniczek¹,

Śnietura²,

Młynarczyk-Liszka³

et al. 2013

pjp

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The aim of the study was to determine expression of the PTEN suppressor gene in colorectal adenocarcinoma and its precancerous lesions (adenomatous polyps) in correlation with common clinical and histopathological features. Forty-four patients with adenomatous polyps and 32 with primary adenocarcinoma of the colon or rectum were enrolled in the study. They underwent endoscopic removal of polyps or major surgery and postoperative adjuvant chemo-and radiotherapy depending on staging of the disease. No patient had received chemotherapy and/or radiotherapy before the surgery. PTEN expression was evaluated using immunohistochemical staining on paraffin-embedded specimens and compared to clinicopathological features of tumors. In colorectal cancers, PTEN expression was found to be significantly lower than in normal intestinal mucosa and adenomatous polyps. That was associated with complete loss of PTEN expression observed more frequently in colorectal cancer, contrary to reduction of PTEN expression occurring mostly in polyps. A correlation between polyp diameter and loss of PTEN was demonstrated as well as between tumor size and TNM advanced stage and PTEN expression. The obtained results suggest that the PTEN/PI3K/Akt pathway may play an important role in early stages of sporadic colorectal carcinogenesis and reduced PTEN expression in late oncogenesis is associated with some adverse clinical and pathological features.

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“…The loss of PTEN protein expression (30% of colorectal tumours) may therefore be an additional factor of PI3K/AKT pathway activation, which may be responsible for resistance to anti-EGFR antibodies, as it was firstly reported in a small series of 27 patients in which PTEN protein expression was evaluated by immunohistochemistry (Frattini et al, 2007). However, subsequent studies have reported discrepant results on the predictive value of loss of PTEN expression (Razis et al, 2008;LaurentPuig et al, 2009;Sartore-Bianchi et al, 2009;Loupakis et al, 2009a), in part, due to the use of different methods for the determination of PTEN status and to the absence of standardization of immunohistochemistry. These findings show that, as for PIK3CA mutations, loss of PTEN expression cannot be currently used as a single marker for prediction of resistance to cetuximab in mCRC patients.…”

Section: Pik3ca Mutations and Loss Of Pten Expressionmentioning

confidence: 99%