PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-10

AUTHORS

M Frattini, P Saletti, E Romagnani, V Martin, F Molinari, M Ghisletta, A Camponovo, L L Etienne, F Cavalli, L Mazzucchelli

ABSTRACT

To evaluate whether the epidermal growth factor receptor (EGFR), K-Ras and PTEN, all members of the EGFR signalling pathway, may affect the clinical response in cetuximab-treated metastatic colorectal cancer (mCRC) patients. Twenty-seven cetuximab-treated mCRC patients were evaluated for drug response and investigated for EGFR protein expression and gene status, K-Ras mutational status and PTEN protein expression. Ten patients achieved a partial response (PR) to cetuximab-based therapy. All 27 patients showed EGFR protein overexpression. Epidermal growth factor receptor gene amplification was observed in eight out of 27 (30%) and chromosome 7 marked polysomy in 16 (59%) patients. Partial response was observed in six out of eight patients with EGFR gene amplification, four out of 16 with marked polysomy and none out of three with eusomy (P<0.05). The K-Ras wild-type sequence was observed in 17 patients, and nine of them experienced a PR. Conversely, K-Ras was mutated in 10 cases, of which one patient experienced a PR (P<0.05). The PTEN protein was normally expressed in 16 patients, and 10 of them achieved a PR. In contrast, no benefit was documented in 11 patients with loss of PTEN activity (P<0.001). Patients with EGFR gene amplification or chromosome 7 marked polysomy respond to cetuximab. In addition to K-Ras mutations, we demonstrate for the first time that the loss of PTEN protein expression is associated with nonresponsiveness to cetuximab. More... »

PAGES

6604009

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6604009

DOI

http://dx.doi.org/10.1038/sj.bjc.6604009

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038401526

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17940504


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