Retrospective RNA Sequencing of Dedifferentiated Liposarcoma Phase II-III Clinical Trial Patients Reveals a Potential Biomarker of Selinexor Response


In this case study, Discovery Life Sciences conducted a retrospective, exploratory RNA sequencing study in collaboration with Karyopharm Therapeutics using FFPE dedifferentiated liposarcoma (DD-LPS) tumor samples collected over the course of a multi-center phase II - III selinexor clinical trial in advanced liposarcoma.  The study design made no a priori prediction or hypothesis about which genes might emerge as potential biomarkers, and instead evaluated the entire ribosomal RNA-reduced transcriptome empirically. The results indicated that the transcript expression of CALB1, a calcium-binding protein with no reported connection to DD-LPS, was associated with resistance to the drug whereas lack of CALB1 transcript expression was associated with improved response to selinexor vs. Placebo.