MiRNA biomarkers for eribulin response

ABSTRACT: Background: Recent phase II and III clinical trials demonstrated antitumor 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 tumor tissue from primary tumors 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 tumor samples and analyzed 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 endpoint of the clinical trial and used as a primary response measure for correlative studies. Seventeen out of 53 (32.1%) evaluable patients in the analyzed subset had non-progressive disease at week 12 and were defined as responders. Results: The expression of 26 individual microRNAs (p<0.05) differed significantly between non-responders and responders. Additional microRNAs of potential relevance were identified when considering the different histological subgroups. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87902 | GEO | 2017/02/20

SECONDARY ACCESSION(S): PRJNA348182

REPOSITORIES: GEO