Blocking autophagy overcomes resistance to dual histone deacetylase and proteasome inhibition in gynecologic cancer.

ABSTRACT: Histone deacetylase (HDAC) inhibitors and proteasome inhibitors have been approved by the FDA for the treatment of multiple myeloma and lymphoma, respectively, but have not achieved similar activity as single agents in solid tumors. Preclinical studies have demonstrated the activity of the combination of an HDAC inhibitor and a proteasome inhibitor in a variety of tumor models. However, the mechanisms underlying sensitivity and resistance to this combination are not well-understood. This study explores the role of autophagy in adaptive resistance to dual HDAC and proteasome inhibition. Studies focus on ovarian and endometrial gynecologic cancers, two diseases with high mortality and a need for novel treatment approaches. We found that nanomolar concentrations of the proteasome inhibitor ix

SUBMITTER: Bi J 

PROVIDER: S-EPMC8763941 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature