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Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Cancer Center Amsterdam, Department of Neurosurgery, VU University Medical Center, Amsterdam ; ThromboDx B.V., Amsterdam.
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2016 (engelsk)Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 1, s. 1066-1075Artikkel i tidsskrift (Fagfellevurdert) Published
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Abstract [en]

Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.

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2016. Vol. 7, nr 1, s. 1066-1075
Emneord [en]
diagnostics, NSCLC, liquid biopsies, platelets, EML4-ALK
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-117842DOI: 10.18632/oncotarget.6279ISI: 000369950300077PubMedID: 26544515OAI: oai:DiVA.org:umu-117842DiVA, id: diva2:915462
Tilgjengelig fra: 2016-03-30 Laget: 2016-03-04 Sist oppdatert: 2018-06-07bibliografisk kontrollert

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