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Silvestris N.,Scientific Institute for Research and Treatment of Cancer Giovanni Paolo II | Tommasi S.,Cancer Institute Giovanni Paolo II | Petriella D.,Cancer Institute Giovanni Paolo II | Santini D.,Biomedical University of Rome | And 6 more authors.
Oncology | Year: 2010

Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR pathway as potential targeted anticancer drugs is encouraging, but this attractive therapy option is still at an early stage of development. Copyright © 2010 S. Karger AG.


Fratto M.E.,Biomedical University of Rome | Santini D.,Biomedical University of Rome | Vincenzi B.,Biomedical University of Rome | Silvestris N.,Scientific Institute for Research and Treatment of Cancer giovanni Paolo II | And 7 more authors.
Frontiers in Bioscience - Scholar | Year: 2011

The key role of epidermal growth factor receptor (EGFR) in tumorigenesis has been demonstrated in several cancer types, so recent clinical trials have investigated their activity/efficacy in different settings. Two different types of EGFR-targeted agents were developed: monoclonal antibodies such as cetuximab and panitumumab, and tyrosine kinase inhibitors, such as gefitinib and erlotinib. In this review, we summarize the preclinical rational of potential activity and the most important clinical trials evaluated anti-EGFR targeted agents in non-colorectal digestive cancer, both in monotherapy and in combination with other chemotherapeutic or targeted agents. Patient selection by use of biologic markers will identify which patients are more likely to respond, contributing to the successful use of these agents.

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