Alterations of ALK may interfere with the biological activity of EGFR through cross-talk of signaling pathways. The discovery of a new potentially relevant oncogenic event in lung cancer, the EML4-ALK translocation, and the development of ALK inhibitors with promising results in preclinical models and randomized clinical trials provides the rationale for the comprehensive characterization of ALK abnormalities in patients with other solid tumors, such as CRC. The identification of additional resistance biomarkers is an unmet clinical need for anti-EGFR treatment personalization in this setting.Īnaplastic lymphoma kinase (ALK) is a member of the insulin receptor family with tyrosine kinase activity, which can activate signal transduction by ligand binding, gene amplification or mutation. However, even in molecularly enriched populations, there is still a relevant subset of non responders. It was previously shown that the response rate to cetuximab reached the value of 41.2% for patients with KRAS, BRAF, NRAS and exon 20 PI3KCA “quadruple wild-type” status. Several resistance biomarkers beyond KRAS were studied in order to improve patients selection. Treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies - cetuximab and panitumumab - improved the outcome of patients with advanced KRAS wild-type colorectal cancer (CRC) in combination with first- or second-line fluoropyrimidine-based chemotherapy or in the setting of chemorefractory disease –. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. 183 that allows taxpayers to allocate 0.5 percent share of their income tax contribution to a research institution of their choice. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported in part by funds obtained through Italian law Law 12 november 2011 n. Received: DecemAccepted: FebruPublished: April 1, 2014Ĭopyright: © 2014 Pietrantonio et al.
PLoS ONE 9(4):Įditor: John Souglakos, University General Hospital of Heraklion and Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece (2014) Gain of ALK Gene Copy Number May Predict Lack of Benefit from Anti-EGFR Treatment in Patients with Advanced Colorectal Cancer and RAS-RAF-PI3KCA Wild-Type Status. Citation: Pietrantonio F, Maggi C, Di Bartolomeo M, Facciorusso MG, Perrone F, Testi A, et al.
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