Systematic Evaluation of GAPs and GEFs Identifies a Targetable Dependency for Hematopoietic Malignancies

In this study, we systematically interrogated GAPs and GEFs in cancer and identified the GAP ARHGAP45 as a dependency shared across blood cancers while dispensable in normal hematopoiesis. Targeting ARHGAP45-expressing cells is achievable via T-cell receptor chimeric antigen receptor T cells directed at an ARHGAP45-derived antigen and small-molecule inhibition of GTPases required upon ARHGAP45 loss.