Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor

Dejan Juric, Pau Castel, Malachi Griffith, Obi L. Griffith, Helen H. Won, Haley Ellis, Saya H. Ebbesen, Benjamin J. Ainscough, Avinash Ramu, Gopa Iyer, Ronak H. Shah, Tiffany Huynh, Mari Mino-Kenudson, Dennis Sgroi, Steven Isakoff, Ashraf Thabet, Leila Elamine, David B. Solit, Scott W. Lowe, Cornelia Quadt, Malte Peters, Adnan Derti, Robert Schegel, Alan Huang, Elaine R. Mardis, Michael F. Berger (), José Baselga () and Maurizio Scaltriti ()
Additional contact information
Dejan Juric: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Pau Castel: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Malachi Griffith: Washington University School of Medicine, 4566 Scott Avenue, St Louis, Missouri 63110, USA
Obi L. Griffith: Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
Helen H. Won: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Haley Ellis: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Saya H. Ebbesen: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Benjamin J. Ainscough: The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
Avinash Ramu: The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
Gopa Iyer: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Ronak H. Shah: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Tiffany Huynh: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Mari Mino-Kenudson: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Dennis Sgroi: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Steven Isakoff: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Ashraf Thabet: Massachusetts General Hospital Cancer Center, 55 Fruit Street
Leila Elamine: Massachusetts General Hospital Cancer Center, 55 Fruit Street
David B. Solit: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Scott W. Lowe: Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Cornelia Quadt: Novartis Pharma AG, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland
Malte Peters: Novartis Pharma AG, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland
Adnan Derti: Oncology Translational Medicine, Novartis Institutes for BioMedical Research
Robert Schegel: Oncology Translational Medicine, Novartis Institutes for BioMedical Research
Alan Huang: Oncology Translational Medicine, Novartis Institutes for BioMedical Research
Elaine R. Mardis: Washington University School of Medicine, 4566 Scott Avenue, St Louis, Missouri 63110, USA
Michael F. Berger: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
José Baselga: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA
Maurizio Scaltriti: Human Oncology and Pathogenesis Program (HOPP), Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, New York 10065, USA

Nature, 2015, vol. 518, issue 7538, 240-244

Abstract: A study of genome evolution in a metastatic breast cancer bearing an activating PIK3CA mutation, following treatment with the PI(3)Kα inhibitor BYL719, shows that all metastatic lesions, when compared to the pre-treatment tumour, had lost a copy of PTEN; parallel genetic evolution of separate sites with different PTEN genomic alterations had led to a convergent PTEN-null phenotype resistant to PI(3)Kα inhibition.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature13948 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:518:y:2015:i:7538:d:10.1038_nature13948

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature13948

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().