Nature Communications (Dec 2022)
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
- Sally J. Adua,
- Anna Arnal-Estapé,
- Minghui Zhao,
- Bowen Qi,
- Zongzhi Z. Liu,
- Carolyn Kravitz,
- Heather Hulme,
- Nicole Strittmatter,
- Francesc López-Giráldez,
- Sampada Chande,
- Alexandra E. Albert,
- Mary-Ann Melnick,
- Bomiao Hu,
- Katerina Politi,
- Veronica Chiang,
- Nicola Colclough,
- Richard J. A. Goodwin,
- Darren Cross,
- Paul Smith,
- Don X. Nguyen
Affiliations
- Sally J. Adua
- Department of Pathology, Yale University School of Medicine
- Anna Arnal-Estapé
- Department of Pathology, Yale University School of Medicine
- Minghui Zhao
- Department of Pathology, Yale University School of Medicine
- Bowen Qi
- Department of Pathology, Yale University School of Medicine
- Zongzhi Z. Liu
- Department of Pathology, Yale University School of Medicine
- Carolyn Kravitz
- Department of Pathology, Yale University School of Medicine
- Heather Hulme
- Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca
- Nicole Strittmatter
- Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca
- Francesc López-Giráldez
- Yale Center for Genome Analysis, Yale University School of Medicine
- Sampada Chande
- Department of Pathology, Yale University School of Medicine
- Alexandra E. Albert
- Department of Cell Biology, Yale School of Medicine
- Mary-Ann Melnick
- Yale Cancer Center, Yale University School of Medicine
- Bomiao Hu
- Department of Pathology, Yale University School of Medicine
- Katerina Politi
- Department of Pathology, Yale University School of Medicine
- Veronica Chiang
- Yale Cancer Center, Yale University School of Medicine
- Nicola Colclough
- DMPK, Early Oncology TDE, AstraZeneca
- Richard J. A. Goodwin
- Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, AstraZeneca
- Darren Cross
- Global Oncology Medical Affairs, AstraZeneca
- Paul Smith
- Bioscience, Early Oncology TDE, AstraZeneca
- Don X. Nguyen
- Department of Pathology, Yale University School of Medicine
- DOI
- https://doi.org/10.1038/s41467-022-34889-z
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
While EGFR-targeted therapies have clinical benefit, drug-resistant brain metastases present a major obstacle. Here, the authors identify a genetic signature in brain metastatic lesions associated with osimertinib resistance and find RhoA to have an important role in the resulting phenotype.
