Fatty Acid Binding Proteins As a Novel Therapeutic Target in Multiple Myeloma

The fatty acid binding protein (FABP) family is instrumental in fatty acid oxidation, lipid shuttling and signal transduction, but the roles of FABPs in multiple myeloma (MM) have not been explored previously, despite these being safely targetable and holding great translational promise. Using the Broad's Cancer Dependency Map (DepMap) Crispr screening tool, we found that MM, and in fact almost every cancer, shows dependency on FABP5. In patient microarray datasets, we found that increased FABP5 expression in MM cells correlates with poor overall survival (OS) and shorter relapse free survival (Zhan et al., 2006., Mulligan et al., 2006., Carrasco et al., 2006). Interestingly, MM cells from “proliferative” (most aggressive) patient subgroups have the highest expression of FABP5 when comparing the molecular MM subtypes (Zhan et al. 2006). We also found that MM cells from relapsed patients have increased FABP5 expression versus newly-diagnosed patients (Chng et al., 2007). Finally, we analyzed 779 patients in the MMRF CoMMpass dataset and confirmed worse progression-free survival (PFS) and OS in patients with higher than mean FABP5 expression levels in their tumor cells (log-rank-value for high vs. low expression