Longevity & AgingDual WEE1 and JAK Inhibition Shows Promise Against Aggressive T-Cell Leukemias and Lymphomas
Mature T-cell leukemias and lymphomas are aggressive cancers with poor outcomes and few targeted options. Researchers assembled genetic data from 1,825 patients and ran it through a molecular tumor board bioinformatic tool to suggest matched drugs. They then screened 70 candidate drugs across 22 T-cell lymphoma cell lines. Inhibitors of WEE1 and CHK1, key cell-cycle and DNA damage response regulators, were broadly cytotoxic. The WEE1 inhibitor adavosertib caused replication stress, premature mitotic entry, DNA damage, and apoptosis, regardless of TP53 status. Combining it with the JAK inhibitor ruxolitinib was most synergistic in cell lines with active JAK/STAT signaling, and the combination also showed activity in patient T-PLL samples. These preclinical findings provide a rationale for clinical testing of this combination in genetically defined subtypes.
