FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2890140176> ?p ?o ?g. }

• W2890140176 endingPage "e246" @default.
• W2890140176 startingPage "e243" @default.
• W2890140176 abstract "Unfortunately, patients with ALK receptor tyrosine kinase (ALK)-positive NSCLC treated with ALK kinase inhibitors inevitably experience development of resistance mediated by complex mechanisms, including ALK receptor tyrosine kinase gene (ALK) mutations, ALK amplification, neuroendocrine transdifferentiation, or activation of alternative signaling pathways.1Rotow J. Bivona T.G. Understanding and targeting resistance mechanisms in NSCLC.Nat Rev Cancer. 2017; 17: 637-658Crossref PubMed Scopus (528) Google Scholar We report the case of a 47-year-old female patient with stage IV NSCLC harboring an echinoderm microtubule associated protein like 4 (EML4)-ALK E20;A20 fusion who was initially treated with four cycles of platinum/pemetrexed until progressive disease. Thereafter, she was treated with crizotinib for 9 months until development of evasive resistance. Subsequently, the patient was primarily resistant to alectinib and ceritinib (Fig. 1A). We analyzed single isolated circulating tumor cells (CTCs) and cell-free total nucleic acids (cfTNA) by low-pass whole genome and targeted next-generation sequencing in longitudinal liquid biopsy samples from this patient (see Fig. 1A and Supplementary Fig. 1A and B; for methods, refer to the Supplement). We obtained low-pass copy number profiles of single isolated CTCs after the patient had experienced development of evasive resistance to crizotinib and shown primary resistance to alectinib (Fig. 1B). Furthermore, we generated additional copy number profiles of CTCs upon development of primary resistance to ceritinib (Fig. 1C). These analyses revealed the presence of an approximately eightfold MNNG HOS Transforming gene (MET) amplification in all evaluable CTCs at both time points (Fig. 2A and B). MET amplification (∼sevenfold) could also be detected in the cfTNA at comparable time points (Supplementary Table 1). Fluorescence in situ hybridization analyses of biopsy samples from a pan-ALK inhibitor–refractory liver metastasis harboring the same EML4-ALK E20;A20 fusion as the pretreatment biopsy sample also showed high-level MET amplification. This MET amplification was not present in the tumor tissue before initiation of treatment and had thus evolved de novo in the patient (Fig. 3A and 3B). Notably, targeted next-generation sequencing of hotspot mutations in 17 cancer-associated genes (Supplementary Table 2) revealed that no ALK or EGFR mutations were present in the CTCs, cfTNA, or liver metastasis. Thus, the gain of the MET amplification was most likely responsible for the evasive resistance to crizotinib. An amplification of the MET gene was described as causing evasive resistance to alectinib after 7 months of response to treatment in one case study in which the patient subsequently responded to crizotinib.2Gouji T. Takashi S. Mitsuhiro T. Yukito I. Crizotinib can overcome acquired resistance to CH5424802: is amplification of the MET gene a key factor?.J Thorac Oncol. 2014; 9: e27-e28Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar It is unlikely that the MET amplification developed during treatment with alectinib because our patient had never responded to this therapy. In addition, the MET amplification prevented a response to ceritinib because neither ceritinib nor alectinib inhibit MET.1Rotow J. Bivona T.G. Understanding and targeting resistance mechanisms in NSCLC.Nat Rev Cancer. 2017; 17: 637-658Crossref PubMed Scopus (528) Google Scholar, 3Kogita A. Togashi Y. Hayashi H. et al.Activated MET acts as a salvage signal after treatment with alectinib, a selective ALK inhibitor, in ALK-positive non-small cell lung cancer.Int J Oncol. 2015; 46: 1025-1030Google Scholar The high degree of MET amplification could have induced pronounced hyperactivation of the kinase, thereby bypassing the capacity of crizotinib to inhibit MET. A similar mechanism of amplification has been described for BRAF.4Shi H. Moriceau G. Kong X. et al.Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance.Nat Commun. 2012; 3: 724Crossref PubMed Scopus (521) Google Scholar Furthermore, we identified an amplification of v-myc avian myelocytomatosis viral oncogene homolog gene (MYC) and a phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation that was present exclusively in CTCs and not in the cfTNA (Supplementary Fig. 2 and Supplementary Table 3). This study shows the clinically relevant gain of a MET amplification in CTCs and cfTNA after treatment with crizotinib inducing primary resistance to ceritinib and alectinib. Our data further underline the potential of liquid biopsies to reflect tumor heterogeneity and inform clinical decision making.5Bardelli A. Pantel K. Liquid biopsies, what we do not know (yet).Cancer Cell. 2017; 31: 172-179Abstract Full Text Full Text PDF PubMed Scopus (312) Google Scholar Dr. Loges is the recipient of a Heisenberg professorship (LO1863/4-1) awarded by the German Research Council and is funded by the Margarete-Clemens Stfitung. Dr. Janning is funded by the Margarete Clemens Stiftung. Dr. Pantel, Dr. Wikman, Dr. Loges, Dr. Riethdorf, and Dr. Janning are supported by CANCER-ID, which is an Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115749, the resources of which consist of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Association EFPIA companies’ in-kind contribution. We thank Mr. Oliver Mauermann and Ms. Jolanthe Kropidlowskifor for technical support. Supplementary Figure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Download .docx (.15 MB) Help with docx files Supplementary Data" @default.
• W2890140176 created "2018-09-27" @default.
• W2890140176 creator A5003339658 @default.
• W2890140176 creator A5004736909 @default.
• W2890140176 creator A5007249612 @default.
• W2890140176 creator A5007339908 @default.
• W2890140176 creator A5007597822 @default.
• W2890140176 creator A5022181207 @default.
• W2890140176 creator A5031528956 @default.
• W2890140176 creator A5039102985 @default.
• W2890140176 creator A5041263791 @default.
• W2890140176 creator A5045732772 @default.
• W2890140176 creator A5048105827 @default.
• W2890140176 creator A5050358104 @default.
• W2890140176 creator A5051265127 @default.
• W2890140176 creator A5054877901 @default.
• W2890140176 creator A5054896139 @default.
• W2890140176 creator A5057053396 @default.
• W2890140176 creator A5060572768 @default.
• W2890140176 creator A5070370956 @default.
• W2890140176 creator A5078288046 @default.
• W2890140176 creator A5078383767 @default.
• W2890140176 creator A5085016405 @default.
• W2890140176 creator A5086499788 @default.
• W2890140176 date "2018-12-01" @default.
• W2890140176 modified "2023-10-17" @default.
• W2890140176 title "Identification of a High-Level MET Amplification in CTCs and cfTNA of an ALK-Positive NSCLC Patient Developing Evasive Resistance to Crizotinib" @default.
• W2890140176 cites W2000545640 @default.
• W2890140176 cites W2004202575 @default.
• W2890140176 cites W2053473615 @default.
• W2890140176 cites W2588807073 @default.
• W2890140176 cites W2765831845 @default.
• W2890140176 doi "https://doi.org/10.1016/j.jtho.2018.08.2025" @default.
• W2890140176 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30205165" @default.
• W2890140176 hasPublicationYear "2018" @default.
• W2890140176 type Work @default.
• W2890140176 sameAs 2890140176 @default.
• W2890140176 citedByCount "17" @default.
• W2890140176 countsByYear W28901401762018 @default.
• W2890140176 countsByYear W28901401762019 @default.
• W2890140176 countsByYear W28901401762020 @default.
• W2890140176 countsByYear W28901401762021 @default.
• W2890140176 countsByYear W28901401762022 @default.
• W2890140176 crossrefType "journal-article" @default.
• W2890140176 hasAuthorship W2890140176A5003339658 @default.
• W2890140176 hasAuthorship W2890140176A5004736909 @default.
• W2890140176 hasAuthorship W2890140176A5007249612 @default.
• W2890140176 hasAuthorship W2890140176A5007339908 @default.
• W2890140176 hasAuthorship W2890140176A5007597822 @default.
• W2890140176 hasAuthorship W2890140176A5022181207 @default.
• W2890140176 hasAuthorship W2890140176A5031528956 @default.
• W2890140176 hasAuthorship W2890140176A5039102985 @default.
• W2890140176 hasAuthorship W2890140176A5041263791 @default.
• W2890140176 hasAuthorship W2890140176A5045732772 @default.
• W2890140176 hasAuthorship W2890140176A5048105827 @default.
• W2890140176 hasAuthorship W2890140176A5050358104 @default.
• W2890140176 hasAuthorship W2890140176A5051265127 @default.
• W2890140176 hasAuthorship W2890140176A5054877901 @default.
• W2890140176 hasAuthorship W2890140176A5054896139 @default.
• W2890140176 hasAuthorship W2890140176A5057053396 @default.
• W2890140176 hasAuthorship W2890140176A5060572768 @default.
• W2890140176 hasAuthorship W2890140176A5070370956 @default.
• W2890140176 hasAuthorship W2890140176A5078288046 @default.
• W2890140176 hasAuthorship W2890140176A5078383767 @default.
• W2890140176 hasAuthorship W2890140176A5085016405 @default.
• W2890140176 hasAuthorship W2890140176A5086499788 @default.
• W2890140176 hasBestOaLocation W28901401761 @default.
• W2890140176 hasConcept C117643217 @default.
• W2890140176 hasConcept C121608353 @default.
• W2890140176 hasConcept C126322002 @default.
• W2890140176 hasConcept C143998085 @default.
• W2890140176 hasConcept C170493617 @default.
• W2890140176 hasConcept C2776232967 @default.
• W2890140176 hasConcept C2776256026 @default.
• W2890140176 hasConcept C2778347629 @default.
• W2890140176 hasConcept C2779220645 @default.
• W2890140176 hasConcept C2779422266 @default.
• W2890140176 hasConcept C2779438470 @default.
• W2890140176 hasConcept C2779750558 @default.
• W2890140176 hasConcept C2780580887 @default.
• W2890140176 hasConcept C42362537 @default.
• W2890140176 hasConcept C502942594 @default.
• W2890140176 hasConcept C71924100 @default.
• W2890140176 hasConceptScore W2890140176C117643217 @default.
• W2890140176 hasConceptScore W2890140176C121608353 @default.
• W2890140176 hasConceptScore W2890140176C126322002 @default.
• W2890140176 hasConceptScore W2890140176C143998085 @default.
• W2890140176 hasConceptScore W2890140176C170493617 @default.
• W2890140176 hasConceptScore W2890140176C2776232967 @default.
• W2890140176 hasConceptScore W2890140176C2776256026 @default.
• W2890140176 hasConceptScore W2890140176C2778347629 @default.
• W2890140176 hasConceptScore W2890140176C2779220645 @default.
• W2890140176 hasConceptScore W2890140176C2779422266 @default.
• W2890140176 hasConceptScore W2890140176C2779438470 @default.
• W2890140176 hasConceptScore W2890140176C2779750558 @default.
• W2890140176 hasConceptScore W2890140176C2780580887 @default.
• W2890140176 hasConceptScore W2890140176C42362537 @default.
• W2890140176 hasConceptScore W2890140176C502942594 @default.

• next