ArticleOncotarget2016
Heterogeneity of resistance mutations detectable by nextgeneration sequencing in TKI-treated lung adenocarcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Tp53 haploinsufficiency is involved in hotspot mutations and cytoskeletal remodeling in gefitinib-induced drug-resistant EGFRCell death discovery · 2023Article
- Heterogeneous distribution ofRespiratory medicine case reports · 2023Article
- Limited effect of afatinib in a non-small cell lung cancer patient harboring an epidermal growth factor receptor K860I missense mutation: A case report.Thoracic cancer · 2021Article
- Clinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers.Nature communications · 2021Article
- Article
- Low T790M relative allele frequency indicates concurrent resistance mechanisms and poor responsiveness to osimertinib.Translational lung cancer research · 2020Article
- Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids.PloS one · 2020Article
- Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity.Oncology letters · 2019Article
- A potential novel therapy for FGFR1-amplified pancreatic cancer with bone metastasis, screened by next-generation sequencing and a patient-derived xenograft model.Oncology letters · 2019Article
- EGFR T790M detection and osimertinib treatment response evaluation by liquid biopsy in lung adenocarcinoma patients with acquired resistance to first generation EGFR tyrosine kinase inhibitors.Diagnostic pathology · 2018Article
- Novel approaches against epidermal growth factor receptor tyrosine kinase inhibitor resistance.Oncotarget · 2018Review
- Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.Molecular cancer · 2018Review
- Histological evolution from primary lung adenocarcinoma harboring EGFR mutation to high-grade neuroendocrine carcinoma.Thoracic cancer · 2018Article
- Comparison of cross-platform technologies for EGFR T790M testing in patients with non-small cell lung cancer.Oncotarget · 2017Review
- Article
- Individualized drug screening based on next generation sequencing and patient derived xenograft model for pancreatic cancer with bone metastasis.Molecular medicine reports · 2017Article
- Molecular mechanisms of therapy resistance in solid tumors: chasing "moving" targets.Virchows Archiv : an international journal of pathology · 2017Review
- Drugging the 'undruggable' cancer targets.Nature reviews. Cancer · 2017Review
- Strategies for monitoring and combating resistance to combination kinase inhibitors for cancer therapy.Genome medicine · 2017Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
EGFR-mutated lung adenocarcinomas routinely develop resistance to tyrosine kinase inhibitors (TKI). To better characterize the relative frequencies of the resistance mechanisms, we analyzed 48 EGFR-mutated TKI-resistant specimens from 41 patients. Next-generation sequencing of post-treatment specimens detected EGFR p.T790M in 31 (79%) of 39 patients, PIK3CA mutations in 10 (26%), EGFR p.S768_V769delinsIL in one, and KRAS p.G12C in one. Five PIK3CA mutations were outside of codons 542, 545, and 1047. Three of four pre-treatment specimens did not carry the PIK3CA mutation found in the post-treatment sample. Small cell carcinoma transformation was identified in four patients; none had p.T790M, including two where p.T790M was identified in the co-existing adenocarcinoma. In p.T790M-mutated specimens, the allele frequency was less than 5% in 24% of cases. p.T790M allele frequency was usually lower than that of the sensitizing mutation indicating that the resistance mutation was present either in a subset of cells or, if the sensitizing mutation was amplified, in a subset of the sensitizing alleles of a dominant clone. Eight patients had multiple resistance mutations, suggesting either multiple separate resistant clones or a single clone harboring multiple resistance mechanisms. PIK3CA mutations appear to be a more significant resistance mechanism than previously recognized.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.