Cancer
Cell culture and mouse studies suggest inhibiting the mRNA-decapping enzyme DCPS could help treat AML. Screening of a CRISPR single-guide RNA (sgRNA) library targeting protein-coding genes and miRNAs in two mouse AML cell lines expressing CRISPR-associated protein 9 (Cas9) identified DCPS as a gene whose knockout decreased cell viability compared with non-targeting sgRNA. In four human AML cell lines, shRNA targeting DCPS or the DCPS inhibitor PF-06687859 decreased proliferation compared with scrambled shRNA or vehicle, respectively. In one of the AML cell lines, the shRNA targeting DCPS or PF-06687859 increased cell cycle arrest and apoptosis. In three patient-derived xenograft (PDX) mouse models of AML, PF-06687859 decreased leukemia burden in the peripheral blood and bone marrow and increased survival compared with vehicle. Next steps could include testing inhibitors of DCPS in additional models of AML...
BCIQ Target Profiles