Therapeutics: BRAF
In vitro and mouse studies suggest modulating BRAF mRNA splicing could help treat Zelboraf-resistant melanoma. About 30% of Zelboraf-resistant melanomas express splice variants of BRAF that lack the Ras-binding domain targeted by the drug. In a Zelboraf-resistant melanoma cell line expressing a BRAF splice variant, small molecule modulators of pre-mRNA splicing decreased levels of the variant and increased sensitivity of the cells to Zelboraf compared with vehicle. In mice bearing melanoma xenografts expressing the BRAF splice variant, a splicing modulator alone or in combination with Zelboraf decreased tumor growth compared with vehicle. Next steps include testing splicing modulators in patient-derived, Zelboraf-resistant melanoma cell lines.
Daiichi Sankyo Co. Ltd., Chugai Pharmaceutical Co. Ltd. and Roche market the BRAF inhibitor Zelboraf vemurafenib to treat melanoma. ...