Therapeutic potential of combined BRAF/MEK blockade in BRAF-wild type preclinical tumor models.

ABSTRACT:

Background

Mounting evidence suggests that RAF-mediated MEK activation plays a crucial role in paradox MAPK (re)activation, leading to resistance and therapeutic failure with agents hitting a single step along the MAPK cascade.

Methods

We examined the molecular and functional effects of single and combined BRAF (dabrafenib), pan-RAF (RAF265), MEK (trametinib) and EGFR/HER2 (lapatinib) inhibition, using Western Blot and conservative isobologram analysis to assess functional synergism, and explored genetic determinants of synergistic interactions. Immunoprecipitation based assays were used to detect the interaction between BRAF and CRAF. The Mann-Whitney U test was used for comparing quantitative variables.

Results

Here we demonstrated that a combination of MEK and BRAF

SUBMITTER: Del Curatolo A 

PROVIDER: S-EPMC6038340 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature