Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

Javier Escudero,Yinyin Wang,Jose Juan Pozo-Kreilinger,Virginia Martinez-Marin,Daniel Bernabeu,Jing Tang,Alejandro Gallego,Andres Redondo,Patricia Ruiz,Yingying Hu,Marta Mendiola,Alberto Berjon,Jaime Feliu,Victoria Heredia-Soto,Eduardo Ortiz-Cruz

doi:10.1186/s12935-021-02337-5

Abstract

BackgroundEribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS).MethodsIn this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity.ResultsEribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS.ConclusionsOur results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.

Highlights

Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS)
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We explored the activity of eribulin in a STS cell line panel: LPS and LMS, which were the target of the phase III clinical trial, and FS, a rare sarcoma, in which eribulin was previously tested in vitro and in xenografts [19]

Summary

Introduction

Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). Soft tissue sarcomas (STSs) represent approximately 1% of all adult cancers. This heterogeneous group of tumours is currently subclassified by the World Health Organization (WHO) into approximately 80 histological subtypes [1]. Liposarcoma (LPS), one of the most common STSs, has been classically subclassified into 4 subtypes: well-differentiated (WDLPS), dedifferentiated (DDLPS), myxoid (MLPS) and pleomorphic (PLPS), the most recent WHO classification has included a fifth. WDLPS and DDLPS together comprise the largest subgroup of liposarcomas, constituting a histologic and behavioural spectrum of one disease, and sharing a genetic alteration: the amplification of the chromosomal region 12q14-15, which involves the MDM2 and CDK4 genes [3]. Adult fibrosarcoma (FS) shows multiple nonspecific chromosomal abnormalities [8]

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