Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.

ABSTRACT:

Background

Despite significant therapeutic advances, multiple myeloma (MM) remains incurable in most patients due to frequent tumor relapse. A major contributor to relapse is clonal heterogeneity, where subclones exhibit distinct mechanisms of therapy resistance, along with the presence of drug-resistant dormant cells. Eliminating these distinct populations, which often coexist in the tumor niche, is clinically challenging. Identifying survival mechanisms shared by drug-resistant proliferating and dormant cells holds potential for the simultaneous elimination of different tumor-repopulating clones.

Methods

To identify shared mechanisms of therapeutic resistance, we analyzed clinical databases and drug-resistant myeloma cell lines. We employed pharmacologic approaches to targ

SUBMITTER: Sabol HM 

PROVIDER: S-EPMC12870532 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature