Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition.

ABSTRACT:

Background

Malignant melanoma is an aggressive tumor type that often develops drug resistance to targeted therapeutics. The production of colony stimulating factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized macrophages and myeloid derived suppressor cells (MDSC), leading to an immune suppressive tumor milieu.

Methods

We used the syngeneic mouse model of BRAF (V600E) -driven melanoma SM1, which secretes CSF-1, to evaluate the ability of the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy of the oncogenic BRAF inhibitor vemurafenib.

Results

Combined BRAF and CSF-1R inhibition resulted in superior antitumor responses compared with either therapy alone. In mice receiving PLX3397 treatment, a dramatic reduction of tumor-infi

SUBMITTER: Mok S 

PROVIDER: S-EPMC4432503 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature