Nature Communications (Apr 2022)
Distinct resistance mechanisms arise to allosteric vs. ATP-competitive AKT inhibitors
- Kristin M. Zimmerman Savill,
- Brian B. Lee,
- Jason Oeh,
- Jie Lin,
- Eva Lin,
- Wei-Jen Chung,
- Amy Young,
- Wennie Chen,
- Monika Miś,
- Kathryn Mesh,
- Jeffrey Eastham,
- Florian Gnad,
- Zhaoshi Jiang,
- Eric W. Stawiski,
- Benjamin Haley,
- Anneleen Daemen,
- Xiaojing Wang,
- Hartmut Koeppen,
- Zora Modrusan,
- Scott E. Martin,
- Deepak Sampath,
- Kui Lin
Affiliations
- Kristin M. Zimmerman Savill
- Department of Molecular Oncology, Genentech Inc.
- Brian B. Lee
- Department of Molecular Oncology, Genentech Inc.
- Jason Oeh
- Department of Molecular Oncology, Genentech Inc.
- Jie Lin
- Department of Molecular Oncology, Genentech Inc.
- Eva Lin
- Department of Molecular Oncology, Genentech Inc.
- Wei-Jen Chung
- Department of Bioinformatics, Genentech Inc.
- Amy Young
- Department of Molecular Oncology, Genentech Inc.
- Wennie Chen
- Department of Research Pathology, Genentech Inc.
- Monika Miś
- Department of Molecular Oncology, Genentech Inc.
- Kathryn Mesh
- Department of Research Pathology, Genentech Inc.
- Jeffrey Eastham
- Department of Research Pathology, Genentech Inc.
- Florian Gnad
- Department of Bioinformatics, Genentech Inc.
- Zhaoshi Jiang
- Department of Bioinformatics, Genentech Inc.
- Eric W. Stawiski
- Department of Bioinformatics, Genentech Inc.
- Benjamin Haley
- Department of Molecular Biology, Genentech Inc.
- Anneleen Daemen
- Department of Bioinformatics, Genentech Inc.
- Xiaojing Wang
- Department of Discovery Chemistry, Genentech Inc.
- Hartmut Koeppen
- Department of Research Pathology, Genentech Inc.
- Zora Modrusan
- Department of Microchemistry, Proteomics, Lipidomics and NGS, Genentech Inc.
- Scott E. Martin
- Department of Molecular Oncology, Genentech Inc.
- Deepak Sampath
- Department of Molecular Oncology, Genentech Inc.
- Kui Lin
- Department of Molecular Oncology, Genentech Inc.
- DOI
- https://doi.org/10.1038/s41467-022-29655-0
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
How resistance to different classes of AKT inhibitors can emerge is unclear. Here, the authors show that resistance to allosteric inhibitors is mainly due to mutation of AKT1 while the ATP competitive resistance is driven by activation of PIM kinases in prostate cancer models.
