English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 &gt; 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 –4 . We found only significant  q -values of &lt; 0.05 in 7 gene alterations;  CDK6 ,  CCNE1, CDK4, CCND3, MET, FGFR4  and  HRAS  which enrich in de novo resistance [range 36–73%] compared to IRs/LTRs [range 4–22%]. Amplification of  CDK4 /6 was significant in de novo resistance, contrary to IRs and LTRs (91%, 27.9% and 0%, respectively). The presence of co-occurrence  CDK4/6  amplification correlated with poor disease outcome with HR of progression-free survival of 3.63 [95% CI 1.80–7.31,  p -value &lt; 0.001]. The presence of  CDK4/6  amplification in pretreatment specimen serves as a predictive biomarker for de novo resistance in sensitizing  EGFR  mutation.

Co-occurrence CDK4/6 amplification serves as biomarkers of de novo EGFR TKI resistance in sensitizing EGFR mutation non-small cell lung cancer