CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy

• DOI: 10.1016/j.phrs.2025.107709
• Publication Date: 2025-03-23T22:58:44Z
• Authors: Bert Luyckx; Maaike Van Trimpont; Fien Declerck; Eleni Staessens; Annick Verhee; Sara T’Sas; Sven Eyckerman; Fritz Offner; Pieter Van Vlierb...; Steven Goossens; Dorien Clarisse; Karolien De Bosscher

Glucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit bone marrow microenvironment to obtain growth and survival signals, resistance glucocorticoid-induced apoptosis emerges, yet underlying mechanisms remain poorly characterized. Here, we identify that chemokine receptor CCR1, together with its main ligand CCL3, plays a pivotal role reducing glucocorticoid sensitivity cells. We show blocking CCR1 signaling antagonist BX471 enhances anti-MM effects dexamethasone cell lines, primary patient material xenograft mouse model. Mechanistically, drug combination shifts balance between pro- antiapoptotic proteins towards deregulates lysosomal proteins. Our findings suggest may play resistance, as GC-induced downregulation mRNA protein is blunted GC-resistance onset Moreover, demonstrate inhibiting partially reverses this providing promising strategy for resensitizing GC treatment.