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.
Authors
- Yuqiao Liu (ORCID: https://orcid.org/0000-0001-8868-9022)
- Christopher R. Vakoc (ORCID: https://orcid.org/0000-0002-1158-7180)
- Jennifer Lewis (ORCID: https://orcid.org/0009-0009-9619-9731)
- Omar Abdel‐Wahab (ORCID: https://orcid.org/0000-0002-3907-6171)
- Xiangyu Pan (ORCID: https://orcid.org/0000-0002-2537-6616)
- Won Jun Kim (ORCID: https://orcid.org/0000-0002-1816-6119)
- Zhendong Cao (ORCID: https://orcid.org/0000-0002-8189-0169)
- Junwei Shi (ORCID: https://orcid.org/0000-0002-8427-6316)
- Mara Monetti (ORCID: https://orcid.org/0009-0006-9778-9010)
- Anthony F. Daniyan (ORCID: https://orcid.org/0009-0002-2742-2281)
- Bingyi Chen (ORCID: https://orcid.org/0000-0001-9525-2021)
- T Fujino (ORCID: https://orcid.org/0000-0003-3444-4198)
- Pu Zhang (ORCID: https://orcid.org/0000-0002-1548-2087)
- Zhuoning Li (ORCID: https://orcid.org/0009-0005-9064-8170)
- Winson Cai (ORCID: https://orcid.org/0000-0001-7121-0986)
- Jahan Rahman (ORCID: https://orcid.org/0000-0001-8755-5890)
- Sanam Shahid (ORCID: https://orcid.org/0000-0003-4281-4910)
- Juliana Ortiz-Pacheco (ORCID: https://orcid.org/0009-0008-7504-8304)
- Jasmine S. Um (ORCID: https://orcid.org/0009-0004-5907-6453)
- Cynthia Castro (ORCID: https://orcid.org/0009-0002-7626-8903)
- Erin Burns (ORCID: https://orcid.org/0009-0006-7931-234X)
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- Cold Spring Harbor Laboratory (US)
- Kettering University (US)
- Weill Cornell Medicine (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1158/2159-8290.cd-25-0299
- Citations
- 3
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 5.31