HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer.

ABSTRACT:

Background

Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies.

Methods

We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations.

Results

Carfilzomib, via proteasome β5 + β2 inhi

SUBMITTER: Besse A 

PROVIDER: S-EPMC11368961 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature