BioCentury
ARTICLE | Distillery Therapeutics

Cancer

March 28, 2017 3:49 PM UTC

In vitro and mouse studies suggest combining Gleevec imatinib with inhibition of c-fos and DUSP1 could help treat CML. In patient peripheral blood monocytes (PBMCs), levels of c-fos and DUSP1 were higher than in hematopoietic stem and progenitor cells (HSPCs) from healthy volunteers. In a mouse model of BCR-ABL oncogene-driven CML, Gleevec plus knockout of fos and DUSP1, or plus c-fos and DUSP1 inhibitor tool compounds, decreased leukemic cell counts in the peripheral blood and bone marrow and increased survival compared with Gleevec plus normal expression of c-fos and DUSP1 or Gleevec plus vehicle. In a patient-derived xenograft (PDX) mouse model of CML, Gleevec plus the c-fos and DUSP1 inhibitors decreased leukemic cell counts in bone marrow compared with Gleevec alone. Next steps include clinical trials of Gleevec plus c-fos and DUSP1 inhibitors in CML...