Liposarcoma (LPS) is one of the most common types of soft tissue sarcoma (STS), including four subtypes: well-differentiated/atypical lipomatous tumor (ALT/WDLPS), dedifferentiated liposarcoma (DDLPS), myxoid/round cell liposarcoma (MLPS/RCLPS) and pleomorphic liposarcoma (PLS). The morphological diversity of LPS reflects the heterogeneity in clinical and biological behavior and sensitivity to chemotherapy.
The study involved six patients affected by low/high grade LPS (1 ALT/WDLPS and DDLPS, 1 DDLPS, 2 MLPS, 1 RCLPS and 1 PLS). Patient-derived primary cultures were established after patient surgery. The cultures were exposed to drugs currently used (e.i. ifosfamide, epirubicin, trabectidin, eribulin) for the treatment of LPS. Drug concentrations were selected according to the human plasma peak in patients with solid tumors. Percentages of cellular survival were assessed by MMT and TUNEL assays.
The results showed the sensitivity of the cultures to chemotherapy. The combination of ifosfamide and epirubicin was the most active regimen and statistically significant among cultures. Ifosfamide did not affect the survival of the cells, except in RCLPS suggesting its role in this LPS subtype. Epirubicin showed a comparable activity of the combination regimen in DDLPS (28%) and RCLPS (14%) while displayed a lesser cytotoxic effect in ALT/WDLPS and DDLPS (83%) and MLPS (65%). Trabectidin had no effect on the cellular survival in DDLPS and an equivalent activity in ALT/WDLPS and DDLPS and MPLS (61% and 65% respectively). In RCLPS exhibited an important activity (28%). Trabectidin showed a higher efficacy in ALT/WDLPS and DDLPS and a similar trend in MLPS compared to epirubicin. Eribulin displayed a comparable activity of trabectidin in ALT/WDLPS and DDLPS (70%), MLPS (68%) and RCLPS (26%) while was more active in DDLPS (83%). Finally, cellular survival of PLS was not affected by all the drugs.
This study provides a rationale for elucidate the role of chemotherapy for all liposarcoma subtypes using patient-derived LPS primary cultures. The improvement in the understanding of the molecular mechanisms in liposarcoma will help in selecting the appropriate treatment with a potential impact in the clinical setting.
Clinical trial identification
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Has not received any funding.
All authors have declared no conflicts of interest.