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Implications of KRAS mutation status for the treatment of metastatic colorectal cancer

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Abstract

Targeted agents have become an integral part of the treatment of a number of malignant diseases and regimens containing agents that disrupt the epidermal growth factor receptor (EGFR) signaling pathway are now considered a standard therapeutic approach for a range of tumor types. Recently, the mutational status of the KRAS gene in tumors was shown to be predictive of outcome to treatment with EGFR-targeted therapies in metastatic colorectal cancer (mCRC). The immoglobulin (Ig) G1 EGFR-targeting monoclonal antibody (mAb), cetuximab, has been shown to provide significant clinical benefits when added to standard irinotecan- and oxaliplatin-containing chemotherapy regimens, first-line, in patients with KRAS wild-type mCRC. Its effects on tumor response and resectability of metastases make cetuximab a particularly useful treatment option for patients with bulky or initially unresectable disease. With an ever-increasing array of management options available, it is important that patients with mCRC receive the treatment that offers them the best chance of prolonged survival. In view of this, testing for tumor KRAS mutation status should be mandatory at diagnosis of mCRC, prior to treatment decision-making.

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Acknowledgements

The authors wish to acknowledge the input of the members of the panel. These were: Ass. Prof. Assen Dudov, Sofia Cancer Center, Sofia, Bulgaria; Ass. Prof. Stjepko Plestina, Clinical Hospital Center, Zagreb, Croatia; Ass. Prof. Evangelos Briassoulis, University Hospital, Ioannina, Greece; Ass. Prof. Demetrios Mavroudis, University Hospital of Heraklion, Crete, Greece; Prof. George Fountzilas, University Hospital of Thessaloniki “Papageorgiou”, Thessaloniki, Greece; Samuel Murray PhD, Head of Molecular Oncology and Genetics, Metropolitan Hospital, Athens, Greece; Prof Baruch Klein, Meir Medical Center, Kfar Saba, Israel; Ass. Prof Tudor Ciuleanu, Institutut Oncologic ‘Ion Chricuta’ Cluj, Cluj Napoca 400015, Romania; Dr Dusan Jovanovic, Institute of Oncology Sremska Kamenica, Novi Sad, Serbia; Dr Jana Ocvirk, Institute of Oncology, Ljubljana, Slovenia: Prof. Gokhan Demir, Florence Nigthingale Hospital, Istanbul, Turkey.

Conflict of interest statement

Although the authors have not received and will not receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript, benefits have been or will be received, but are directed solely to a research fund, foundation, educational institution or other non-profit organization with which one or more of the author(s) is associated.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Experimental and Clinical Medicine and Surgery F. Magrassi and A. Lanzara, Second University of Naples, Naples, Italy

    Fortunato Ciardiello

  2. Digestive Oncology Unit, Centre for Human Genetics, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium

    Sabine Tejpar

  3. Department of Medical Oncology, BOC Oncology Center, Nicosia, Cyprus

    Demetris Papamichael

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  1. Fortunato Ciardiello
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  2. Sabine Tejpar
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  3. Demetris Papamichael
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Correspondence to Fortunato Ciardiello.

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Ciardiello, F., Tejpar, S. & Papamichael, D. Implications of KRAS mutation status for the treatment of metastatic colorectal cancer. Targ Oncol 4, 311–322 (2009). https://doi.org/10.1007/s11523-009-0129-6

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  • DOI: https://doi.org/10.1007/s11523-009-0129-6

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