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BIOMARKER:

MAP2K1 P124

i
Other names: MAP2K1, MAPKK1, MEK1, PRKMK1, Mitogen-activated protein kinase kinase 1
Entrez ID:
Related biomarkers:
1year
A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
P1b, N=6, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2027 --> Oct 2023 | Trial primary completion date: Sep 2027 --> Oct 2023
Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
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fulvestrant • mirdametinib (PD-0325901)
over1year
A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
P1b, N=6, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=150 --> 6
Enrollment closed • Enrollment change • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
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fulvestrant • mirdametinib (PD-0325901)
over1year
A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer (clinicaltrials.gov)
P1b, N=150, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Sep 2027
Trial completion date • Trial primary completion date • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
|
ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
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fulvestrant • mirdametinib (PD-0325901)
almost2years
Concordance of Actionable Mutations in Liquid Biopsies and Matched Tumor Tissue of Brazilian Non-small Cell Lung Cancer (NSCLC) (LALCA 2023)
The NGS panel could successfully detect actionable mutations in liquid biopsies with a high concordance rate and sensitivity. The detection of variants in cfDNA, but not in tDNA, suggests a greater representativeness of the mutational tumor spectrum in samples of liquid biopsies opening perspectives for employing this approach in the routing setting. The NGS assay for liquid biopsy may decrease tissue biopsies and turnaround time for report release, accelerating therapeutic strategies for NSCLC patients.
Liquid biopsy • Biopsy • Discordant
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EGFR (Epidermal growth factor receptor) • 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) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
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KRAS G12C • EGFR T790M • KRAS G12D • KRAS G12V • KRAS G13D • KRAS G12 • PIK3CA E542K • KRAS G13 • TP53 R175H • KRAS Q61H • ALK R1275Q • BRAF G469A • EGFR E709K • MAP2K1 P124Q • PIK3CA E542 • TP53 R248Q • TP53 Y220C • EGFR E746 • MAP2K1 E203K • MAP2K1 P124 • TP53 R273C
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Oncomine™ Lung cfDNA Assay
over2years
Investigating the Retained Inhibitory Effect of Cobimetinib against p.P124L Mutated MEK1: A Combined Liquid Biopsy and in Silico Approach. (PubMed, Cancers (Basel))
The samples at different time points were collected from a BRAF-mutant melanoma patient who developed an early resistance to dabrafenib/trametinib...With an in silico modeling, we identified cobimetinib as an alternative MEK inhibitor, and consequently suggested a therapy switch to vemurafenib/cobimetinib...The cobimetinib administration led to an important reduction in the BRAF p.V600E and MEK1 p.P124L allele fractions and in the CMC number, features suggestive of a putative response. In summary, this study emphasizes the usefulness of a liquid biopsy-based approach combined with in silico simulation, to track real-time tumor evolution while assessing the best treatment option.
Journal • Liquid biopsy
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MAP2K1 (Mitogen-activated protein kinase kinase 1)
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BRAF V600E • BRAF V600 • MAP2K1 P124L • MAP2K1 P124
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Mekinist (trametinib) • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • Cotellic (cobimetinib)
3years
[VIRTUAL] Mutation Detection in Circulating Tumor Cells at the SingleCell Level Using the MassARRAY System (AMP 2021)
We have established a novel, straightforward protocol to detect mutation directly from CTC without preamplification at the single cell level. We expect that this workflow will facilitate the exploration of genetic content of CTC, thereby increasing its potential use in the clinic
Circulating tumor cells
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
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BRAF V600E • NRAS mutation • BRAF V600 • EGFR T790M • PIK3CA H1047R • KRAS G12V • NRAS Q61K • KRAS G12 • NRAS Q61 • NRAS Q61R • MAP2K1 P124S • MAP2K1 C121S • KRAS Q61K • MAP2K1 P124 • CDK4 mutation
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CELLSEARCH® • Parsortix Liquid Biopsy
3years
Clinical • New P1 trial • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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ER positive • HR positive • HER-2 negative • MAP2K1 mutation • MAP2K1 P124L • MAP2K1 P124S • MAP2K2 mutation • MAP2K1 C121S • MAP2K1 F53L • MAP2K1 K57N • MAP2K1 P124
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fulvestrant • mirdametinib (PD-0325901)
almost4years
Computational Study on the Effect of Inactivating/Activating Mutations on the Inhibition of MEK1 by Trametinib. (PubMed, Int J Mol Sci)
Hence, trametinib could dissociate from the active mutants (P124S and E203K) more easily compared with the WT MEK1. In summary, our theoretical results demonstrated that the active mutations may attenuate the inhibitory effects of MEK inhibitor (trametinib) on MEK1, which could be crucial clues for future anti-cancer treatment.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
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KRAS mutation • ALK positive • MAP2K1 mutation • EGFR positive • MAP2K1 P124S • MAP2K1 E203K • MAP2K1 P124
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Mekinist (trametinib)
4years
Circulating Tumour DNA Sequencing Identifies a Genetic Resistance-Gap in Colorectal Cancers with Acquired Resistance to EGFR-Antibodies and Chemotherapy. (PubMed, Cancers (Basel))
Our results support the utility of ctDNA-Seq to guide treatment allocation for patients with resistance and the importance of investigating further non-canonical EGFR-Ab resistance mechanisms, such as microenvironmentally-mediated resistance. The detection of MAP2K1 mutations could inform trials of MEK-inhibitors in these tumours.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
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KRAS mutation • HER-2 amplification • HER-2 mutation • MAP2K1 mutation • MAP2K1 P124S • MAP2K1 P124
4years
[VIRTUAL] The Association Between MAP2K1 Mutation Class and Clinical Features in MAP2K1‑Mutant East Asian Non‑Small Cell Lung Cancer Patients (IASLC-WCLC 2020)
Briefly, patients with (n=9) or without (n=5) co-occurring TP53 mutations had a median OS of 12.0 months and not up to now respectively (P=0.41); patients with (n=3) or without (n=11) co-occurring KRAS mutations had a median OS of not up to now and 12.0 months respectively (P=0.33); patients with (n=4) or without (n=10) co-occurring KRAS mutations had a median OS of 14.5 months and 12.0 months respectively (P=0.57); patients with (n=4) or without (n=23) co-occurring STK11 mutations had a median OS of 11.5 months and 12.0 months respectively (P=0.70). Conclusion MAP2K1 genetic alter occurs in a subset of NSCLC, and improved understanding of the implications of MAP2K1 aberrations is critical for the identification of therapeutic target candidates.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MSH6 (MutS homolog 6)
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TP53 mutation • STK11 mutation • MAP2K1 P124L • MAP2K1 P124