Abstract 3757
Background
Eribulin has an effect on proliferation, migration and invasion of sarcoma and breast cancer in vitro assays. A phase III clinical trial in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) showed an improvement in overall survival (OS) for the eribulin arm compared to dacarbazine, although no benefit was observed in the LMS restricted subgroup. Based on these results, eribulin was approved only for advanced LPS patients. The aim of the current study is to evaluate the effect of eribulin on key cell properties, like proliferation, migration, and invasion in LMS cell lines, in conventional 2D, but also 3D culture models.
Methods
Eribulin was kindly provided by Eisai Inc. (Andover, USA) and tested on CP0024 and SK-UT-1 human LMS cell lines. Cellular proliferation was determined by SRB assay on 2D, and measured by spheroid diameter and by propidium iodide and calcein-AM double staining in 3D cultures by Celigo Platform (Nexcelom, Lawrence, USA).Cells were treated with increased concentrations of eribulin to determine IC50 values and its effect on proliferation. Chemotaxis and invasion were determined using transwell assay on 2D culture. Spheroids grown during 4 days were laid or embedded in matrigel for 3D assays and quantified over 3-7 additional days.
Results
Both cell lines had a mesenchymal-like appearance on monolayer culture, although SK-UT-1 had a more compact spheroid pattern compared to CP0024. Proliferation, migration, and invasion were examined after exposure to eribulin. The results showed that eribulin is active on both cell lines inhibiting proliferation in 2 and 3D culture conditions at concentrations below the nanomolar range. Moreover, eribulin significantly inhibited migration and invasion. To our knowledge, these findings are the first to demonstrate the effect of eribulin in LMS cell line 3D models.
Conclusions
Our results support the in vitro activity of eribulin in LMS cell lines and its further exploration as an agent with clinical benefit in patients with LMS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Eisai.
Disclosure
M. Mendiola: Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai. A. Gallego Martínez: Travel / Accommodation / Expenses, Non-remunerated activity/ies, training courses: Eisai. A. Redondo: Honoraria (self), Research grant / Funding (institution): Eisai. All other authors have declared no conflicts of interest.
Resources from the same session
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract