Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway.

ABSTRACT:

Background

Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance.

Methods

Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs).

Results

Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an

SUBMITTER: Qi F 

PROVIDER: S-EPMC8418008 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature