Autophagy inhibition overcomes sorafenib resistance in S45F-mutated desmoid tumors.

ABSTRACT:

Background

Desmoid tumors (DTs) are rare and understudied fibroblastic lesions that are frequently recurrent and locally invasive. DT patients often experience chronic pain, organ dysfunction, decrease in quality of life, and even death.

Methods

Sorafenib has emerged as a promising therapeutic strategy, which has led to the first randomized phase 3 clinical trial devoted to DTs. Concurrently, we conducted a comprehensive analysis of sorafenib efficacy in a large panel of desmoid cell strains to probe for response mechanism.

Results

We found distinctive groups of higher- and lower-responder cells. Clustering the lower-responder group, we observed that CTNNB1 mutation was determinant of outcome. Our results revealed that a lower dose of sorafenib was able to inhibit cel

SUBMITTER: Braggio D 

PROVIDER: S-EPMC6625904 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature