Related Experiment Video
Updated: Jul 17, 2026
Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Published on: June 13, 2018
Preclinical Evaluation of Liposomal Eribulin (E7389-LF) in a Panel of Sarcoma Patient-Derived Xenograft Models
Misato Jinno1, Shigehiro Yagishita1, Shoraku Ryu1
1National Cancer Center Research Institute Tokyo Japan.
Abstract:
Sarcomas are rare, heterogeneous tumors with poor prognoses, underscoring the urgent need for novel therapies. Liposomal eribulin (E7389-LF) was developed to improve the efficacy and safety profile of eribulin; however, its preclinical evaluation in sarcomas remains limited. This study aimed to evaluate the clinical applicability of E7389-LF. E7389-LF was comprehensively evaluated and compared with eribulin using 12 patient-derived xenograft (PDX) models representing six sarcoma subtypes. Antitumor activity was assessed across five treatment groups, including independently scaled, clinically relevant regimens of eribulin (0.47 mg/kg) and E7389-LF (0.77 mg/kg). Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry and fluorescence immunostaining. In addition, correlations between antitumor activity and clinical efficacy were descriptively investigated. Treatment with E7389-LF (0.77 mg/kg) induced tumor regression in 7 of 12 models (58%), compared with 4 of 12 models (33%) treated with eribulin (0.47 mg/kg). Notable responses were observed in rhabdomyosarcoma, Ewing sarcoma, and leiomyosarcoma models. No apparent weight loss was observed in either treatment group. Pharmacokinetic analyses indicated increased systemic and intratumoral drug exposure with E7389-LF. In three PDX models derived from patients treated with eribulin, tumor responses reflected the corresponding clinical outcomes, providing preliminary evidence for the translational relevance of these models. This study demonstrates that E7389-LF exerts antitumor activity broadly comparable to eribulin and exerts antitumor activity in several models across sarcoma PDX models, with favorable tolerability and improved intratumoral drug retention. These findings support the clinical development of E7389-LF for patients with sarcoma who have limited treatment options.
Insights
Liposomal eribulin (E7389-LF) shows promising antitumor activity in preclinical sarcoma models, comparable to eribulin but with improved drug retention. This supports further clinical development for sarcoma patients.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Sarcomas are rare, aggressive cancers with limited treatment options.
- Novel therapeutic strategies are urgently needed to improve patient outcomes.
- Eribulin is an established chemotherapy agent, but liposomal formulation (E7389-LF) may enhance its efficacy and safety.
Purpose of the Study:
- To evaluate the preclinical antitumor activity and clinical applicability of liposomal eribulin (E7389-LF) in diverse sarcoma patient-derived xenograft (PDX) models.
- To compare the efficacy and tolerability of E7389-LF with conventional eribulin.
- To assess the pharmacokinetic profile and translational relevance of sarcoma PDX models.
Main Methods:
- Utilized 12 sarcoma PDX models across six subtypes.
- Administered E7389-LF (0.77 mg/kg) and eribulin (0.47 mg/kg) in five treatment groups.
- Assessed antitumor activity, including tumor regression.
- Conducted pharmacokinetic analyses using liquid chromatography-tandem mass spectrometry and fluorescence immunostaining.
- Investigated correlations between preclinical activity and clinical outcomes in PDX models from previously treated patients.
Main Results:
- E7389-LF induced tumor regression in 58% (7/12) of models, versus 33% (4/12) for eribulin.
- Significant responses were observed in rhabdomyosarcoma, Ewing sarcoma, and leiomyosarcoma models.
- E7389-LF demonstrated increased systemic and intratumoral drug exposure with favorable tolerability (no significant weight loss).
- PDX models showed preliminary translational relevance, mirroring clinical responses to eribulin.
Conclusions:
- Liposomal eribulin (E7389-LF) exhibits potent preclinical antitumor activity in a broad range of sarcoma subtypes.
- E7389-LF offers comparable efficacy to eribulin with improved pharmacokinetic properties and tolerability.
- These findings strongly support the further clinical investigation of E7389-LF for patients with advanced sarcoma.
