Article ; Online: Co-occurrence CDK4/6 amplification serves as biomarkers of de novo EGFR TKI resistance in sensitizing EGFR mutation non-small cell lung cancer.
2022 Volume 12, Issue 1, Page(s) 2167
Abstract: Despite the development of predictive biomarkers to shape treatment paradigms and outcomes, de novo EGFR TKI resistance advanced non-small cell lung cancer (NSCLC) remains an issue of concern. We explored clinical factors in 332 advanced NSCLC who ... ...
| Abstract | Despite the development of predictive biomarkers to shape treatment paradigms and outcomes, de novo EGFR TKI resistance advanced non-small cell lung cancer (NSCLC) remains an issue of concern. We explored clinical factors in 332 advanced NSCLC who received EGFR TKI and molecular characteristics through 65 whole exome sequencing of various EGFR TKI responses including; de novo (progression within 3 months), intermediate response (IRs) and long-term response (LTRs) (durability > 2 years). Uncommon EGFR mutation subtypes were significantly variable enriched in de novo resistance. The remaining sensitizing EGFR mutation subtypes (exon 19 del and L858R) accounted for 75% of de novo resistance. Genomic landscape analysis was conducted, focusing in 10 frequent oncogenic signaling pathways with functional contributions; cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGF-β, p53 and β-catenin/Wnt signaling. Cell cycle pathway was the only significant alteration pathway among groups with the FDR p-value of 6 × 10 |
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| MeSH term(s) | Aged ; Antineoplastic Agents/therapeutic use ; Biomarkers ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Cyclin-Dependent Kinase 4/genetics ; Cyclin-Dependent Kinase 6/genetics ; Drug Resistance, Neoplasm ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; Female ; Gene Amplification ; Genes, erbB-1 ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Male ; Middle Aged ; Progression-Free Survival ; Protein Kinase Inhibitors/therapeutic use ; Treatment Outcome |
| Chemical Substances | Antineoplastic Agents ; Biomarkers ; Protein Kinase Inhibitors ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; CDK4 protein, human (EC 2.7.11.22) ; CDK6 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22) ; Cyclin-Dependent Kinase 6 (EC 2.7.11.22) |
| Language | English |
| Publishing date | 2022-02-09 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-022-06239-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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