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

Cancer Cell International

Marta Mendiola¹  Virginia Martinez-Marin²  Alejandro Gallego²  Eduardo Ortiz-Cruz³  Daniel Bernabeu⁴  Patricia Ruiz⁵  Alberto Berjon⁶  Jose Juan Pozo-Kreilinger⁶  Yinyin Wang⁷  Yingying Hu⁷  Jing Tang⁷  Javier Escudero⁸  Victoria Heredia-Soto⁹  Jaime Feliu^1,10  Andres Redondo^1,11 

[1] Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, 28046, Madrid, Spain;Molecular Pathology and Therapeutic Targets Group, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046, Madrid, Spain;Department of Medical Oncology, Hospital Universitario La Paz, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain;Department of Orthopaedic Surgery, Hospital Universitario La Paz, IdiPAZ, 28046, Madrid, Spain;Department of Radiology, Hospital Universitario La Paz, IdiPAZ, 28046, Madrid, Spain;Molecular Pathology and Therapeutic Targets Group, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046, Madrid, Spain;Molecular Pathology and Therapeutic Targets Group, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), Paseo de la Castellana, 261, 28046, Madrid, Spain;Department of Pathology, Hospital Universitario La Paz, IdiPAZ, 28046, Madrid, Spain;Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland;Translational Oncology Research Laboratory, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28046, Madrid, Spain;Translational Oncology Research Laboratory, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28046, Madrid, Spain;Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, 28046, Madrid, Spain;Translational Oncology Research Laboratory, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28046, Madrid, Spain;Center for Biomedical Research in the Cancer Network (Centro de Investigación Biomédica en Red de Cáncer, CIBERONC), Instituto de Salud Carlos III, 28046, Madrid, Spain;Department of Medical Oncology, Hospital Universitario La Paz, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain;Cátedra UAM-ANGEM, Faculty of Medicine, Universidad Autónoma de Madrid, Paseo de La Castellana, 261, 28046, Madrid, Spain;Translational Oncology Research Laboratory, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), 28046, Madrid, Spain;Department of Medical Oncology, Hospital Universitario La Paz, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain;Cátedra UAM-ANGEM, Faculty of Medicine, Universidad Autónoma de Madrid, Paseo de La Castellana, 261, 28046, Madrid, Spain;

关键词: Eribulin;    Sarcoma;    Proliferation;    Migration;    Invasion;    2D and 3D models;   

DOI  :  10.1186/s12935-021-02337-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY