Evaluating the impact of CRBN mutations on response to immunomodulatory drugs and novel cereblon E3 ligase modulators in myeloma.

ABSTRACT:

Abstract

Immunomodulatory drug (IMiD) resistance is a key clinical challenge in myeloma treatment. Previous data suggest almost one-third of myeloma patients acquire genetic alteration of the key IMiD effector cereblon (CRBN) by the time they are pomalidomide refractory. Some events, including stop codons/frameshift mutations and copy loss, have clearly explicable effects on CRBN protein function. Missense mutations have also been reported throughout the length of CRBN but their functional impact has not been systematically studied. This study modeled selected missense mutations and examined their effect on CRBN function also analyzing whether any mutations deleterious to IMiD action could be overcome using the novel cereblon E3 ligase modulators (CELMoDs). Three patterns of respon

SUBMITTER: Chrisochoidou Y 

PROVIDER: S-EPMC12824623 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature