News - MAP2K1 K57E - LARVOL VERI

2years

Evaluation of somatic and germline variants in patients with small bowel adenocarcinoma reveals clinically actionable targets. (ASCO 2022)

Of the entire cohort, we observed five activating PIK3CA mutations (R108H; G364R; E542K; E545K, n = 2) which may be sensitive to FDA-approved PIK3CA inhibitor alpelisib. Additionally, patients with loss-of-function mutation in NF1 (n = 2), STK11 (n = 1) and PTEN (n = 1) can be targeted with MEK inhibitor selumetinib and mTOR inhibitor everolimus, respectively. Except for one V600E mutation, all mutations in BRAF are either type 2 (L597R, n = 1) or type 3 (N581S, n = 1; D594N, n = 4) which were sensitive to MEK inhibitor trametinib...Interestingly, one IDH1 mutation (R132C) carrier in our cohort might benefit from ivosidenib... Through comprehensive genomic characterization of Chinese SBA patients, we identified actionable variants of multiple signaling pathways in plenty. NGS profiling results can guide physicians to enroll a significant portion of SBA patients in genomically-matched clinical trials.

2 years ago

Clinical • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3) • ARID2 (AT-Rich Interaction Domain 2) • FAT3 (FAT Atypical Cadherin 3) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • SOX9 (SRY-Box Transcription Factor 9) • SPTA1 (Spectrin Alpha)

TP53 mutation • BRAF V600E • KRAS mutation • HER-2 amplification • PIK3CA mutation • BRAF V600 • IDH1 mutation • PTEN mutation • STK11 mutation • PIK3CA E545K • NF1 mutation • HER-2 S310F • HER-2 V777L • PIK3CA E542K • IDH1 R132C • PIK3CA E545 • BRAF L597R • HER-2 V842I • IDH1 R132 • PIK3CA E542 • BRAF D594N • MAP2K1 F53L • MAP2K1 K57E • MAP2K1 K57N • BRAF L597 • HER-2-H

Onco PanScan™

Mekinist (trametinib) • everolimus • Koselugo (selumetinib) • Piqray (alpelisib) • Tibsovo (ivosidenib)

3years

[VIRTUAL] Genomic profiling of small bowl adenocarcinoma reveals targetable mutations in multiple signaling pathways (AACR 2021)

We also found two MAP2K1 activating mutations (K57E and K57N) which can be targeted by trametinib...We also observed two activating PIK3CA mutations (R108H and G364R) which may be sensitive to PIK3CA inhibitor alpelisib... The mutational landscape of our SBA cohort provided compelling evidence that multiple signaling pathways play a role in the pathogenesis of SBA and many driver mutations in these pathways are targetable. Our findings indicated that SBA patients should participate in matched clinical trials for better management of this disease.

3 years ago

Tumor Mutational Burden

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MLH1 (MutL homolog 1) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • KMT2C (Lysine Methyltransferase 2C) • FGF3 (Fibroblast growth factor 3) • ARID2 (AT-Rich Interaction Domain 2) • FAT3 (FAT Atypical Cadherin 3) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • ZKSCAN1 (Zinc Finger With KRAB And SCAN Domains 1)

TP53 mutation • BRAF V600E • KRAS mutation • HER-2 amplification • PIK3CA mutation • BRAF V600 • HER-2 V777L • BRAF L597R • HER-2 V842I • MET fusion • MAP2K1 K57E • MAP2K1 K57N • BRAF L597

Mekinist (trametinib) • Piqray (alpelisib)

over3years

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma. (PubMed, Sci Rep)

This study revealed multiple genetic, proteomic and phosphoproteomic alterations associated with erlotinib resistant SCC-R cells. Our data indicates that therapeutic targeting of MAPK pathway is an effective strategy for treating erlotinib-resistant HNSCC tumors.

over 3 years ago

Journal

EGFR (Epidermal growth factor receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • AXL (AXL Receptor Tyrosine Kinase) • YAP1 (Yes associated protein 1)

MAP2K1 K57E

erlotinib