Identification of microRNA biomarkers for response of advanced soft tissue sarcomas to eribulin: Translational results of the EORTC 62052 trial
Autor: | Agnieszka Wozniak, Herman Burger, Axelle Nzokirantevye, Erik A.C. Wiemer, Marcel Smid, Raf Sciot, Patrick Schöffski, Stefan Sleijfer, Giuseppe Floris |
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Přispěvatelé: | Medical Oncology |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Oncology Leiomyosarcoma Adult Male Cancer Research medicine.medical_specialty Pathology Adolescent Phases of clinical research Antineoplastic Agents Liposarcoma Disease-Free Survival 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Internal medicine microRNA medicine Biomarkers Tumor Humans Furans Aged Aged 80 and over business.industry Soft tissue sarcoma Sarcoma Ketones Middle Aged medicine.disease Clinical trial MicroRNAs 030104 developmental biology Treatment Outcome chemistry 030220 oncology & carcinogenesis Female business Neoplasms Connective and Soft Tissue Eribulin |
Zdroj: | European Journal of Cancer, 75, 33-40. Elsevier Ltd. |
ISSN: | 1879-0852 0959-8049 |
Popis: | Background Recent phase II and III clinical trials demonstrated anti-tumour activity of eribulin, a tubulin-interacting cytotoxic agent, in patients with metastatic soft tissue sarcoma (STS). In this exploratory study, we aimed to identify putative microRNA biomarkers that associate with eribulin sensitivity or resistance in STS. Materials and methods Archival tumour tissue from primary tumours or metastatic lesions was collected prior to eribulin treatment, from 65 consenting patients involved in the EORTC trial 62052. This phase II study ( ClinicalTrials.gov identifier NCT00413192 ) included multiple subtypes of STS. Tissue was available from 21 leiomyosarcomas, 14 adipocytic sarcomas, 9 synovial sarcomas and 21 other sarcoma histotypes. Total RNA was isolated from formalin-fixed, paraffin-embedded tumour samples and analysed using Taqman® Low Density Arrays to determine microRNA expression profiles. The expression of a total of 756 microRNAs was assessed. Progression-free survival at week 12 (RECIST 1.0) measured as a binary variable, was the primary end-point of the clinical trial and used as a primary response measure for correlative studies. Seventeen of 53 (32.1%) evaluable patients in the analysed subset had non-progressive disease at week 12 and were defined as responders. Results The expression of 26 individual microRNAs (p Conclusions The expression level of particular microRNAs in STS tissue samples may predict response to eribulin. Further validation studies as well as a preclinical assessment of the underlying molecular mechanisms are required. |
Databáze: | OpenAIRE |
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