Advertisement

 

 

Preclinical Evaluation of Vemurafenib as Therapy for BRAFMutated Sarcomas.

Preclinical Evaluation of Vemurafenib as Therapy for BRAFMutated Sarcomas.
Author Information (click to view)

Gouravan S, Meza-Zepeda LA, Myklebost O, Stratford EW, Munthe E,


Gouravan S, Meza-Zepeda LA, Myklebost O, Stratford EW, Munthe E, (click to view)

Gouravan S, Meza-Zepeda LA, Myklebost O, Stratford EW, Munthe E,

Advertisement

International journal of molecular sciences 2018 03 2319(4) pii E969
Abstract

The BRAFmutation, which in melanoma is targetable with vemurafenib, is also found in sarcomas and we here evaluate the therapeutic potential in sarcoma cell lines.

METHODS
Four sarcoma cell lines harboring the BRAFV600E mutation, representing liposarcomas (SA-4 and SW872), Ewing sarcoma (A673) and atypical synovial sarcoma (SW982), were treated with vemurafenib and the effects on cell growth, apoptosis, cell cycle progression and cell signaling were determined.

RESULTS
Vemurafenib induced a strong cytostatic effect in SA-4 cells, mainly due to cell cycle arrest, whereas only moderate levels of apoptosis were observed. However, a high dose was required compared to BRAFmutated melanoma cells, and removal of vemurafenib demonstrated that the continuous presence of drug was required for sustained growth inhibition. A limited growth inhibition was observed in the other three cell lines. Protein analyses demonstrated reduced phosphorylation of ERK during treatment with vemurafenib in all the four sarcoma cell lines confirming that the MAPK pathway is active in these cell lines, and that the pathway can be inhibited by vemurafenib, but also that these cells can proliferate despite this.

CONCLUSIONS
These findings indicate that vemurafenib alone would not be an efficient therapy against BRAFmutated sarcomas. However, further investigations of combination with other drugs are warranted.

Submit a Comment

Your email address will not be published. Required fields are marked *

18 − sixteen =

[ HIDE/SHOW ]