News - MAP2K1 K57T - LARVOL VERI

1year

Clonal mutation burden and evolutionary dynamics analysis in metastatic gastro-esophageal adenocarcinoma (GEA) by error corrected whole-exome circulating tumor DNA sequencing (AACR 2023)

A MEK1 K57T mutation evolved at resistance in a HER2 amplified EGA treated with trastuzumab+chemotherapy, demonstrating the utility to identify mechanisms of acquired resistance. ctDNA WES can assess the genetics of entire metastatic cancer cell populations over time and deconvolute their evolutionary trajectories... ctDNA WES can assess the genetics of entire metastatic cancer cell populations over time and deconvolute their evolutionary trajectories. 43% pts had higher cMB in ctDNA compared to biopsies. Liquid biopsy analyses by WES may be superior to tissue-based WES for mutation burden analysis and neoantigen vaccine designs.

1 year ago

Tumor mutational burden • IO biomarker • Circulating tumor DNA • Metastases

HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

HER-2 amplification • MAP2K1 K57T

Herceptin (trastuzumab)

almost2years

Molecular mechanisms underlying the resistance of BRAF V600E-mutant metastatic colorectal cancer to EGFR/BRAF inhibitors. (PubMed, Ther Adv Med Oncol)

Multiple genetic alterations are associated with clinical benefits and resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC. Our findings provide novel insights into strategies for overcoming resistance to EGFR/BRAF inhibitors in patients with BRAF V600E-mutant mCRC.

almost 2 years ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RNF43 (Ring Finger Protein 43) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)

BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • KRAS G12D • KRAS G12 • NRAS Q61 • KRAS Q61H • NRAS G12D • RNF43 mutation • NRAS G12 • NRAS Q61L • MAP2K1 K57T • BRAF amplification • KRAS Q61L

almost2years

Natural distribution of genomic alterations correlated with the resistance to KRASG12C inhibitor in Chinese colorectal cancer. (ASCO 2022)

Novel acquired secondary KRAS mutations within the adagrasib-binding pocket such as Y96C, H95D/Q/R, R68S, 2... Our analysis results indicate about 15% KRAS G12C-mutant Chinese CRC were probable resistant to KRASG12C inhibitor. One-third of these patients had co-existed oncogenic fusions and higher TMB levels, suggesting possibilities for other therapeutic choices.

almost 2 years ago

Tumor Mutational Burden

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NRG1 (Neuregulin 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • ETV6 (ETS Variant Transcription Factor 6) • EWSR1 (EWS RNA Binding Protein 1) • IKZF3 (IKAROS Family Zinc Finger 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GRB7 (Growth Factor Receptor Bound Protein 7) • TCF7L2 (Transcription Factor 7 Like 2) • TPM4 (Tropomyosin 4) • PAX7 (Paired Box 7)

TP53 mutation • BRAF V600E • KRAS mutation • TMB-H • PIK3CA mutation • BRAF V600 • MET amplification • KRAS G12D • ALK fusion • NRAS Q61K • NRAS Q61 • KRAS Q61H • NRAS G12D • FGFR3 fusion • NRAS G13 • MAP2K1 K57T • FGFR3 amplification • KRAS Q61K

Krazati (adagrasib)