Rational drug combination design in patient-derived avatars reveals effective inhibition of hepatocellular carcinoma with proteasome and CDK inhibitors.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) remains difficult to treat due to limited effective treatment options. While the proteasome inhibitor bortezomib has shown promising preclinical activity in HCC, clinical trials of bortezomib showed no advantage over the standard-of-care treatment sorafenib, highlighting the need for more clinically relevant therapeutic strategies. Here, we propose that rational drug combination design and validation in patient-derived HCC avatar models such as patient-derived xenografts (PDXs) and organoids can improve proteasome inhibitor-based therapeutic efficacy and clinical potential.

Methods

HCC PDXs and the corresponding PDX-derived organoids (PDXOs) were generated from primary patient samples for drug screening and efficacy studies. To ident

SUBMITTER: Lim JJ 

PROVIDER: S-EPMC9377092 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature