News - EGFR E746_A750del

9ms

Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration (AACR 2024)

We also present a case demonstrating a favorable response to the dual therapy of olaparib and osimertinib in NSCLC harboring EGFR, RAD50, and ARID1A mutations that progressed on osimertinib. There were 2298 patients in the NSCLC cohort (MSKCC database). HRD aberrations are uncommon in EGFR mutated lung cancer patients. Further investigation on the role of PARP inhibitor in EGFR mutated lung cancer is warranted.

9 months ago

PARP Biomarker • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • RAD50 (RAD50 Double Strand Break Repair Protein)

BRCA2 mutation • BRCA1 mutation • EGFR mutation • EGFR exon 19 deletion • HRD • ARID1A mutation • EGFR E746_A750del • HRD + BRCA1 mutation • RAD50 mutation • EGFR E746

Guardant360® CDx

Lynparza (olaparib) • Tagrisso (osimertinib)

2years

High-Definition PCR (HDPCR) Detection of Precision Biomarkers in Non-Small Cell Lung Cancer Samples (AMP 2022)

This HDPCR prototype assay includes relevant research biomarkers in current National Comprehensive Cancer Network (NCCN) guidelines, including variants in EGFR, BRAF, KRAS, ERBB2, ALK, ROS1, RET, MET, and NTRK1/2/3, and has shown sensitive and specific performance. In addition, this assay leverages a proprietary bioinformatics suite, the ChromaCode Cloud, to report relevant variants with the click of a button, allowing for an easily adopted solution to testing needs.

2 years ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)

EGFR mutation • KRAS G12C • EGFR L858R • EGFR exon 20 insertion • KRAS G12 • EGFR E746_A750del • EGFR exon 20 mutation • EGFR E746

over2years

Efficacy of osimertinib in patients with EGFR mutant lung cancer harboring the uncommon exon 19 deletion, L747_A750>P. (ASCO 2022)

The del19 mutation L747_A750 > P is associated with inferior PFS compared to the common E746_A750del mutation in pts treated with 1L osimertinib. Understanding differences in osimertinib efficacy among EGFR del19 subtypes could alter management of these pts in the future.

over 2 years ago

Clinical

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR exon 19 deletion • EGFR T790M • EGFR E746_A750del • EGFR E746 • EGFR L747_A750>P

Tagrisso (osimertinib)

over2years

Next-generation sequencing revealed clonal architecture and faciliated diagnosis of patients with multiple lung tumors: An analysis of 12 cases (AACR 2022)

However, caution is warranted when NGS detects no aberration from any of the multiple sequenced nodules. Examination of the mutational landscape found that altered proto-oncogene KRAS was associated with smaller tumors whereas altered tumor suppressors TP53 and CDKN2A associated with smaller ones, suggesting different roles in these molecules play in tumor growth.

over 2 years ago

Clinical • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • GNAS (GNAS Complex Locus)

KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ALK fusion • EGFR E746_A750del • EGFR G719A • EGFR exon 18 mutation • EGFR E746

over3years

Epiregulin confers EGFR-TKI resistance via EGFR/ErbB2 heterodimer in non-small cell lung cancer. (PubMed, Oncogene)

Among the EGFR ligands, EREG significantly diminished cellular sensitivity to TKIs and was associated with decreased response to erlotinib in NSCLC patients...EREG induced the formation of the EGFR/ErbB2 heterodimer regardless of gefitinib treatment...In addition, EREG-enriched macrophage conditional medium induced EGFR-TKI resistance. These findings shed new light on the mechanism underlying EGFR-TKI resistance, and suggest macrophage-produced intratumoral EREG as a novel regulator and biomarker for EGFR-TKI therapy in NSCLC.

over 3 years ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • EREG (Epiregulin)

EGFR mutation • EGFR E746_A750del • EREG overexpression • EGFR E746

erlotinib • gefitinib