Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients
California Institute for Regenerative Medicine · Stanford University · +8 more institutions
Abstract
Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in
Citation impact
- FWCI
- 37.99
- Percentile
- 100%
- References
- 66
Authors
22- JJJacob J. ChabonCorresponding
California Institute for Regenerative Medicine, Stanford University
- ADAndrew D. Simmons
Clovis Oncology (United States)
- AFAlexander F. Lovejoy
California Institute for Regenerative Medicine, Stanford University
- MSMohammad Shahrokh Esfahani
California Institute for Regenerative Medicine, Stanford University
- AMAaron M. Newman
California Institute for Regenerative Medicine, Stanford University
Topics & keywords
- KRAS
- Crizotinib
- T790M
- Osimertinib
- Epidermal growth factor receptor
- EGFR inhibitors
- Lung cancer
- Medicine
- Good health and well-being