Aug. 29 Preclinical Quick Takes: New targets for leukemia from Calico and stroke from Gero; predictors of checkpoint inhibitor response and more
Calico finds new target for sensitizing leukemia to NK cells
Calico Life Sciences LLC (South San Francisco, Calif.) showed in an eLife paper that blocking DCAF15, an adaptor for E3 ubiquitin ligase substrates, could boost the sensitivity of leukemia to antitumor NK cell activity. DCAF15 deletion upregulated the lymphocyte costimulatory molecule CD80 in chronic myelogenous leukemia (CML) cells, resulting in amplified cell death when cocultured with NK cells. Reduced DCAF15 was associated with increased survival in AML patients.
Gero Discovery links cancer target to stroke, neurological diseases
Gero Discovery LLC (Moscow, Russia) and colleagues discovered that PFKFB3, which has been linked to solid tumors, can be inhibited to treat stroke. In a Scientific Reports paper, the team showed AZ67, a small molecule PFKFB3 inhibitor, prevents neuronal cell death stemming from stress induced by glycolysis activation. In mice, AZ67 improved motor coordination and decreased brain infarct volume after ischemic injury. AZ67 also protected cultured neurons from apoptosis triggered by a β amyloid fragment, suggesting it could be used to treat Alzheimer's disease...