Targeting EGFR and PI3K pathways in ovarian cancer
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Le résumé fourni par la source
BACKGROUND: The epidermal growth factor receptor (EGFR) is expressed in ovarian cancer, but agents targeting this pathway have shown little effect as single agents. This may be due to the presence of alternative pathways, particularly activation of the PI3K/Akt/MTOR pathway. METHODS: We have therefore examined the effect of inhibitors of this pathway (ZSTK474 and sirolimus) in combination with the EGFR inhibitors erlotinib and gefitinib in ovarian cancer primary cell cultures. RESULTS: The single-agent EGFR inhibitors showed little activity, although some activity was seen with the single-agent PI3K inhibitor, ZSTK474. Combinations of ZSTK474 with EGFR inhibitors showed enhanced activity with some evidence of synergy, whereas sirolimus combinations were less active. The results were not explicable on the basis of PIK3CA mutation or amplification, or PTEN loss, although one tumour with a KRAS mutation showed resistance to EGFR inhibitors. However, there was correlation of the EGFR expression with sensitivity to EGFR and resistance to PI3K active agents, and inverse correlation in the sensitivity of individual tumours to agents active against these pathways, suggesting a mechanism of action for the combination. CONCLUSION: Phase I/II clinical trials with these agents should include further pharmacodynamic endpoints and molecular characterisation to identify patients most likely to benefit from this strategy.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Targeting EGFR and PI3K pathways in ovarian cancer
- Date Crossref
- 10/09/2013
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Queen Alexandra Hospital pays non établi dans la noticeÉtablissement de santé
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Sheffield Children's NHS Foundation Trust Sheffield Diagnostic Genetics Service pays non établi dans la noticeÉtablissement de santé
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Horizon Discovery (United Kingdom) pays non établi dans la noticeEntreprise
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University Hospitals Coventry and Warwickshire NHS Trust Department of Pathology pays non établi dans la noticeÉtablissement de santé
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Translational Oncology Research Centre pays non établi dans la noticeStructure de recherche
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Horizon Discovery Ltd pays non établi dans la noticeEntreprise
Queen Alexandra Hospital, Sheffield Diagnostic Genetics Service — Sheffield Children's NHS Foundation Trust et Horizon Discovery (United Kingdom), avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.