The BIM deletion polymorphism is associated with apoptosis resistance to EGFR-TKIs, such as gefitinib and erlotinib, in EGFR mutated lung cancer. Tanimoto and colleagues report that the BIM deletion polymorphism is sufficient to confer resistance to the third-generation TKI, osimertinib. They further identified HDAC3 as an important regulator of BIM pre-mRNA splicing, and that pan-HDAC inhibitor vorinostat overcomes BIM deletion polymorphism associated EGFR-TKI resistance via inhibition of HDAC3. These findings illustrate the importance of developing selective HDAC3 inhibitors, and provide the rationale for combined use of HDAC3 inhibitors with osimertinib in EGFR-mutated lung cancer carrying the BIM deletion polymorphism.
The mechanisms that allow tumor cells to escape immunosurveillance are not well understood. Pereira and colleagues found recurrent inactivating mutations in the invariant light chain of the HLA-I complex, B2M in lung cancer. Furthermore, they found alterations at CALR, PDIA3, and TAP1, which are involved in the maturation of the HLA-I...
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