Abstract 2736
Background
Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering the mesenchymal-to-epithelial (MET) transition. Previously we reported that eribulin-induced MET was associated with re-sensitization of resistant HNSCC cell lines to cetuximab. In this study, we evaluated eribulin activity in preclinical R/M HNSCC models.
Methods
In vitro antiproliferative activities (IC50) were determined in three human HNSCC cell lines (OSC-20, OSC-19 and OLC01) treated with eribulin or other microtubule inhibitors (paclitaxel and vinblastine). The effects of eribulin were evaluated in eribulin-sensitive and -resistant HNSCC xenograft tumors.
Results
Eribulin demonstrate selectively high sensitivity to OLC01 cells (R/M HNSCC) in comparison with other cell lines. Eribulin has sub-0.1 nM growth inhibitory activities in vitro against OLC01 cells as well as marked in vivo activities at 0.1–0.5 mg/kg against OLC01 cells xenografts. Inducible TUBB3 correlates with lower sensitivity to eribulin in HNSCC cells and xenograft tumors.
Conclusions
Understanding the mechanisms involved in the overall drug response to eribulin may help in the design of therapeutic strategies that enhance drug activity and improve benefits of eribulin in R/M HNSCC patients.
Clinical trial identification
Legal entity responsible for the study
Graduate School of Medical Science, Kanazawa University.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.