Unknown

Dataset Information

0

Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma.


ABSTRACT: Resistance to epidermal growth factor receptor (EGFR)-targeted therapy is insufficiently understood in head and neck squamous cell carcinoma (HNSCC), entailing the lack of predictive biomarkers.Here, we studied resistance-mediating EGFR ectodomain and activating RAS mutations by next-generation sequencing (NGS) of cell lines and tumor tissue of cetuximab-naïve patients (46 cases, 12 cell lines), as well as liquid biopsies taken during and after cetuximab/platinum/5-fluorouracil treatment (20 cases). Tumors of cetuximab-naïve patients were unmutated, except for HRAS mutations in 4.3% of patients. Liquid biopsies revealed acquired KRAS, NRAS or HRAS mutations in more than one third of patients after cetuximab exposure. 46% of patients with on-treatment disease progression showed acquired RAS mutations, while no RAS mutations were found in the non-progressive subset of patients, indicating that acquisition of RAS mutant clones correlated significantly with clinical resistance (Chi square p=0.032). The emergence of mutations preceded clinical progression in half of the patients, with a maximum time from mutation detection to clinical progression of 16 weeks.RAS mutations account for acquired resistance to EGFR-targeting in a substantial proportion of HNSCC patients, even though these tumors are rarely mutated at baseline. Liquid biopsies may be used for mutational monitoring to guide treatment decisions.

SUBMITTER: Braig F 

PROVIDER: S-EPMC5190002 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma.

Braig Friederike F   Voigtlaender Minna M   Schieferdecker Aneta A   Busch Chia-Jung CJ   Laban Simon S   Grob Tobias T   Kriegs Malte M   Knecht Rainald R   Bokemeyer Carsten C   Binder Mascha M  

Oncotarget 20160701 28


Resistance to epidermal growth factor receptor (EGFR)-targeted therapy is insufficiently understood in head and neck squamous cell carcinoma (HNSCC), entailing the lack of predictive biomarkers.Here, we studied resistance-mediating EGFR ectodomain and activating RAS mutations by next-generation sequencing (NGS) of cell lines and tumor tissue of cetuximab-naïve patients (46 cases, 12 cell lines), as well as liquid biopsies taken during and after cetuximab/platinum/5-fluorouracil treatment (20 cas  ...[more]

Similar Datasets

2011-01-14 | GSE21483 | GEO
2011-01-14 | E-GEOD-21483 | biostudies-arrayexpress
| S-EPMC5471055 | biostudies-literature
| S-EPMC8664160 | biostudies-literature
2012-12-01 | GSE36790 | GEO
2012-12-01 | E-GEOD-36790 | biostudies-arrayexpress
2023-07-19 | GSE156554 | GEO
| S-EPMC5496455 | biostudies-literature
| S-EPMC6294373 | biostudies-literature
| S-EPMC7352434 | biostudies-literature