Nature Communications (Apr 2022)
AKT mutant allele-specific activation dictates pharmacologic sensitivities
- Tripti Shrestha Bhattarai,
- Tambudzai Shamu,
- Alexander N. Gorelick,
- Matthew T. Chang,
- Debyani Chakravarty,
- Elena I. Gavrila,
- Mark T. A. Donoghue,
- JianJong Gao,
- Swati Patel,
- Sizhi Paul Gao,
- Margaret H. Reynolds,
- Sarah M. Phillips,
- Tara Soumerai,
- Wassim Abida,
- David M. Hyman,
- Alison M. Schram,
- David B. Solit,
- Lillian M. Smyth,
- Barry S. Taylor
Affiliations
- Tripti Shrestha Bhattarai
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Tambudzai Shamu
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Alexander N. Gorelick
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Matthew T. Chang
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Debyani Chakravarty
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
- Elena I. Gavrila
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Mark T. A. Donoghue
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
- JianJong Gao
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
- Swati Patel
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Sizhi Paul Gao
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Margaret H. Reynolds
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- Sarah M. Phillips
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
- Tara Soumerai
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- Wassim Abida
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- David M. Hyman
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- Alison M. Schram
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- David B. Solit
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Lillian M. Smyth
- Department of Medicine, Memorial Sloan Kettering Cancer Center
- Barry S. Taylor
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- DOI
- https://doi.org/10.1038/s41467-022-29638-1
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 11
Abstract
How different oncogenic Akt mutants can affect the response to Akt inhibitors is currently unclear. Here, the authors analyse somatic mutations of Akt1-3 isoforms in several human cancers, investigate their oncogenic effects and therapeutic relevance in vitro and confirm some of their data in a clinical trial testing the AKT inhibitor capivasertib in patients with solid tumors harboring AKT alterations.