Cereblon isoforms and their use as biomarkers for therapeutic treatment

摘要

Provided herein are cereblon isoforms and methods of their use as biomarkers for treating a disease, disorder, or condition with a treatment compound, e.g., thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)-piperidine-2,6-dione, or (S)-3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione.

主权项

1. A method for determining whether a subject having a multiple myeloma is sensitive to a treatment with pomalidomide or a pharmaceutically acceptable salt thereof, wherein said method comprises
(a) obtaining a multiple myeloma sample from the subject; (b) determining the level of an isoform of CRBN in the multiple myeloma sample, the isoform of CRBN comprising a single exon 6 deletion and comprising exons 1-5 and 7-11; (c) diagnosing the subject as being sensitive to the treatment with pomalidomide or a pharmaceutically acceptable salt thereof if the isoform of CRBN was determined to be less than a baseline level in the multiple myeloma sample; and (d) administering an effective amount of pomalidomide or a pharmaceutically acceptable salt thereof to the subject diagnosed as being sensitive to the treatment with pomalidomide or a pharmaceutically acceptable salt thereof.