Cancer

Patient sample, cell culture and mouse studies suggest combining ribosomal 30S subunit inhibitors or other inhibitors of oxidative phosphorylation with Gleevec imatinib could help treat CML. In leukemic hematopoietic stem cells (HSCs) from patients, fatty acid oxidation and mitochondrial respiration were higher than in HSCs from healthy volunteers. In the primary leukemic HSCs, the ribosomal 30S subunit inhibitor Tygacil tigecycline decreased proliferation, colony formation, mitochondrial respiration and oxidative phosphorylation compared with vehicle, and Tygacil plus Gleevec decreased proliferation and colony formation compared with either agent alone. In a xenograft mouse model of CML, Tygacil plus Gleevec decreased leukemic HSC numbers compared with either agent alone. Next steps include testing other oxidative phosphorylation inhibitors in CML models, in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL), and other leukemias.

Novartis AG markets the BCR-ABL tyrosine kinase (BCR-ABL) inhibitor Gleevec for CML and several other hematologic malignancies and cancers...