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    DRUG CLASS:

    MAP3K1 inhibitor

    Related drugs:
    11ms
    Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer. (PubMed, Kaohsiung J Med Sci)
    Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early-onset CRC development, combined with novel functional analyses and omics approaches.
    Journal
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    MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    1year
    MAP3K1 expression is associated with progression and poor prognosis of hormone receptor-positive, HER2-negative early-stage breast cancer. (PubMed, Cell Oncol (Dordr))
    Our results indicate that the overexpression of MAP3K1 plays a major role in the poor prognosis of HR-positive, HER2-negative early stage breast cancer.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • MMP9 (Matrix metallopeptidase 9) • CCNB1 (Cyclin B1) • MAPK8 (Mitogen-activated protein kinase 8)
    |
    HR positive • HER-2 negative • EGFR positive • HR positive + HER-2 negative
    |
    docetaxel • tamoxifen • doxorubicin hydrochloride
    1year
    Asperulosidic Acid Restrains Hepatocellular Carcinoma Development and Enhances Chemosensitivity Through Inactivating the MEKK1/NF-κB Pathway. (PubMed, Appl Biochem Biotechnol)
    Furthermore, the effect of ASPA (100 μg/mL) on the sensitivity of HCC cells to chemotherapeutic agents, including doxorubicin and cisplatin, was evaluated. In vivo results displayed that ASPA substantially curbed tumor growth and inactivated the MEKK1/NF-κB pathway in mice. All over, ASPA exerts antitumor effects in HCC by suppressing the MEKK1/NF-κB pathway.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    cisplatin • doxorubicin hydrochloride
    1year
    Dexamethasone activates c-Jun NH2-terminal kinase (JNK) which interacts with GR and protects it from ubiquitin-mediated degradation in NSCLC cells. (PubMed, Biochem Biophys Res Commun)
    Further, GR protein levels were significantly decreased in JNK inhibitor (JNKi, SP600125) treated cells whereas MG132 treatment restored GR levels indicating that DEX induced JNK activity regulated the GR protein levels through proteasomal-degradation pathway. In line with these in vitro data, patient dataset analysis also shows that increased levels of both JNK and GR contributes towards better prognosis of NSCLC patients. Taken together, our data shows that DEX treatment may lead to positive feedback regulation of GR by activating JNK and thus highlights importance of GR-JNK crosstalk in NSCLC.
    Journal
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    MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
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    dexamethasone • MG132 • SP600125
    over1year
    Early Triple-Negative Breast Cancers in a Singapore Cohort Exhibit High PIK3CA Mutation Rates Associated With Low PD-L1 Expression. (PubMed, Mod Pathol)
    Analysis of comutation frequencies further revealed that PIK3CA mutations tended to be accompanied by MAP kinase pathway mutation. The mechanism and impact of PIK3CA alterations on the TNBC tumor immune microenvironment and PD-L1 positivity warrant further study.
    Journal • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    PD-L1 expression • TP53 mutation • PIK3CA mutation • PD-L1 negative • PD-L1-L
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
    over1year
    Molecular characterization of advanced primary cardiac sarcomas (Sarcoma-RC 2023)
    All patients gained clinical benefit by first-line doxorubicin-based chemotherapy (2 partial responses, 2 stable disease), although disease control was short-lived (<10 months)...The somatic NGS analysis was consistent with the genomic profile of soft tissue sarcomas and cfDNA analysis was demonstrated for the first time in this rare tumor type to be a potential tool for dynamic tracking of clinical outcome. Legal entity responsible for the study The authors.
    Tumor mutational burden • BRCA Biomarker • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • MTAP (Methylthioadenosine Phosphorylase) • MDM2 (E3 ubiquitin protein ligase) • KMT2D (Lysine Methyltransferase 2D) • PTCH1 (Patched 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC2 (TSC complex subunit 2) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • NOTCH3 (Notch Receptor 3) • EP300 (E1A binding protein p300) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • IRS2 (Insulin receptor substrate 2) • MAPK1 (Mitogen-activated protein kinase 1) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • CCND3 (Cyclin D3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • CTNNA1 (Catenin Alpha 1) • EPHB4 (EPH receptor B4) • RAD52 (RAD52 Homolog DNA Repair Protein) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • ALOX12B (Arachidonate 12-Lipoxygenase) • FANCC (FA Complementation Group C) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    TMB-L • MDM2 amplification • RET mutation • MET mutation • PTCH1 mutation • FANCA mutation • TSC2 mutation • TP53 R196*
    |
    FoundationOne® CDx
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    doxorubicin hydrochloride
    over1year
    Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry. (PubMed, Genome Med)
    Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10), demonstrating the importance of diversifying study cohorts.
    Journal
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    ER (Estrogen receptor) • FGFR2 (Fibroblast growth factor receptor 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    over1year
    Sex-dependent associations between MAP3K1 gene polymorphisms and soy products with the gastric cancer risk in Korea: a case-control study. (PubMed, BMC Gastroenterol)
    Men with the risk allele of MAP3K1 had a significantly increased GC risk compared to GG homozygotes; this trend was more pronounced in those with low intake of soy products.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    over1year
    K-RAS Associated Gene-Mutation-Based Algorithm for Prediction of Treatment Response of Patients with Subtypes of Breast Cancer and Especially Triple-Negative Cancer. (PubMed, Cancers (Basel))
    The novel 12-Gene algorithm based on multitude gene-mutation profiles identified through ML has a potential to predict breast cancer treatment response to therapies, especially in triple-negative subgroups patients, which may assist personalized therapies and reduce mortality.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • RAS (Rat Sarcoma Virus) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
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    TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation
    over1year
    Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma. (PubMed, Sci Rep)
    In advanced setting, in the IDH1m group, the presence of KRAS/NRAS and TP53 mutations negatively impact PFS, whereas the presence of TP53 and PIK3CA mutations negatively impact OS; in the IDH1wt group, only the presence of MTAP mutation negatively impact PFS, whereas the presence of TP53 mutation negatively impact OS. We highlighted several molecular differences with distinct prognostic implications between IDH1m and IDH1wt patients.
    Journal • BRCA Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH2 (Notch 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component)
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    TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • IDH1 mutation • ATM mutation • FGFR2 mutation • CDKN2A mutation • PBRM1 mutation • CDKN2B mutation • IDH wild-type • MTAP mutation • NBN mutation
    |
    FoundationOne® CDx
    over1year
    Recurrent KMT2C Mutations As Clonal Hematopoiesis Is Common after Chemotherapy Exposure in Hodgkin's Lymphoma Patients (ASH 2022)
    Peripheral mononuclear cell samples obtained from 19 HL patients treated at our center with ICI (14 nivolumab only, 1 pembrolizumab only, and 4 both) were sequenced. Prior studies have demonstrated that KMT2C deletions enhance hematopoietic stem cell self-renewal and do give a fitness advantage in the presence of chemotherapy. None of the patients in our cohort has developed therapy-related MDS/AML though it could be a risk in the future.
    Clinical • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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    DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • MSH3 (MutS Homolog 3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • FCGR3A (Fc Fragment Of IgG Receptor IIIa) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • HNF1A (HNF1 Homeobox A)
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    KMT2C mutation • MLL3 deletion • MLL3 mutation
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    Keytruda (pembrolizumab) • Opdivo (nivolumab)
    over1year
    Monogenic and Polygenic Contributions to Venous Thromboembolism (VTE) and Splanchnic Thrombosis in Patients (pts) with Pancreatic Cancer (PC) (ASH 2022)
    Implementation of PC-PRS and integration with somatic data may provide a more refined risk estimation of VTE risk in PC than current clinical tools permit. Further validation in independent cohorts is warranted.
    Clinical
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    over1year
    Genomic and Transcriptomic Landscape of HER2-Low Breast Cancer (SABCS 2022)
    With some exceptions, H2L breast cancer shared genomic features with its more classically defined subset of either HR+ or HRneg disease. Notable differences in PIK3CA (an actionable mutation) and TP53 (a prognostic alteration) warrant additional assessment, as do amplifications variable between HR+H2L and HR+Her2pos groups. Our findings add tremendously to the current understanding of the molecular profile of the H2L subgroup and comparison to the classically defined breast cancer subgroups.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • RNF43 (Ring Finger Protein 43) • CDH1 (Cadherin 1) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • CLTC (Clathrin Heavy Chain) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • DDX5 (DEAD-Box Helicase 5) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
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    PD-L1 expression • HER-2 positive • TP53 mutation • TMB-H • HR positive • HER-2 amplification • PIK3CA mutation • PTEN mutation • CCND1 amplification • HER-2 amplification + PD-L1 expression
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    over1year
    Genomic characterisation of hormone receptor-positive, HER2-negative breast cancer arising in young women: a secondary analysis of the SOFT trial (SABCS 2022)
    The SOFT clinical trial randomised 3066 premenopausal women with HR+ EBC to adjuvant endocrine therapy with tamoxifen alone, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS for 5 years...Younger women aged < 40 years (N=359) compared with women aged ≥ 40 years (N=917) had significantly higher frequencies of mutations in GATA3 (19% vs 16%) and CN amplifications (47% vs 26%), but significantly lower frequencies of mutations in PIK3CA (32% vs 47%), CDH1 (3% vs 9%), and MAP3K1 (7% vs 12%). Additionally, there were significantly higher frequencies of genomic features suggestive of HRD (27% vs 21%), and a higher proportion of younger patients with PIK3CA mutations with concurrent CN amplifications (23% vs 11%).
    Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • HRD • FGFR1 amplification • CCND1 amplification • HR positive + HER-2 negative • GATA3 mutation
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    tamoxifen
    over1year
    Genomic Landscape of Mixed-Phenotype Acute Leukemia. (PubMed, Int J Mol Sci)
    Finally, we show that those patients that received stem cell transplant had a better overall survival. Our findings support the need to genomically profile MPAL cases to exploit opportunities for targeted therapies in this orphan disease with dismal prognosis.
    Journal
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • WT1 (WT1 Transcription Factor) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • MAP3K6 (Mitogen-Activated Protein Kinase Kinase Kinase 6)
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    TP53 mutation • FLT3-ITD mutation • KMT2D mutation
    over1year
    HDLBP promotes hepatocellular carcinoma proliferation and sorafenib resistance by suppressing Trim71-dependent RAF1 degradation. (PubMed, Cell Mol Gastroenterol Hepatol)
    Our study reveals that HDLBP is an important mediator that stabilizes the RAF1 protein and maintains its activity, leading to HCC progression and sorafenib resistance. Thus, HDLBP might represent a potential biomarker and future therapeutic target for HCC.
    Journal
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    MAP2K1 (Mitogen-activated protein kinase kinase 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • TRIM7 (Tripartite Motif Containing 7)
    |
    sorafenib
    over1year
    A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of E6201 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=55, Completed, Eisai Inc. | Unknown status --> Completed
    Trial completion • Metastases
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    BRAF (B-raf proto-oncogene)
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    E6201
    over1year
    Tumor genomic landscape in older women with metastatic breast cancer (MBC) (SABCS 2022)
    "In a large cohort of pts with MBC, the mutational and copy number landscape for older pts differs from that in younger pts, even after controlling for tumor subtype. Key actionable findings include a higher proportion of high TMB and PIK3CA-mutated tumors, emphasizing the importance of genomic profile testing in this pt population and further exploration of efficacy and tolerability of relevant therapies in those age >70 years."
    Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TET2 (Tet Methylcytosine Dioxygenase 2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • HER-2 amplification • HER-2 negative • PIK3CA mutation • TET2 mutation • BRIP1 mutation • BRCA mutation
    |
    OncoPanel™ Assay
    over1year
    Genomic characterization of hormone receptor-positive advanced breast cancer with high tumor mutational burden: fresh-frozen tissue genomic analysis from MUTATION-1 study (KCSG BR17-04) (SABCS 2022)
    Patients who met upper 30% of TMB were eligible for treatment phase and received durvalumab plus tremelimumab. Conclusions The high TMB in HR+ breast cancer was associated with longer time duration from MBC diagnosis to biopsy, high APOBEC signature, and cell cycle/MYC signature gene upregulation. Further therapeutic targeting of high TMB patients is warranted based on their genomic and immunologic characteristics.
    Tumor Mutational Burden • PD(L)-1 Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3) • E2F1 (E2F transcription factor 1)
    |
    TP53 mutation • TMB-H • HR positive • PIK3CA mutation • ARID1A mutation • TMB-L
    |
    Imfinzi (durvalumab) • Imjudo (tremelimumab)
    over1year
    Differential gene mutation landscape in patients With PIK3CA-altered and non-altered hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the SOLAR-1 clinical study (SABCS 2022)
    Alpelisib (ALP), an α- selective PI3K inhibitor and degrader, demonstrated clinical benefit in combination with fulvestrant (FUL) in the SOLAR-1 study in pts with PIK3CA-mut HR+, HER2− ABC. A differential genomic landscape was observed in PIK3CA-alt and PIK3CA-non- alt populations. Clinical benefit of ALP vs PBO was observed in pts with PIK3CA-alt disease who also had alterations in analyzed genes and/or genes associated with the MAPK pathway. The data from this analysis suggest that, of the genes analyzed, only PIK3CA mutations can predict pt sensitivity to ALP.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • ARID1A (AT-rich interaction domain 1A) • RAD51C (RAD51 paralog C) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    HR positive • HER-2 negative • PIK3CA mutation • EGFR positive
    |
    FoundationOne® CDx
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    Piqray (alpelisib) • fulvestrant
    over1year
    NOTCH signaling limits the response of Low Grade Serous Ovarian Cancers to MEK inhibition. (PubMed, Mol Cancer Ther)
    We found that the combination of pan-RAFi with MEKi downregulated HES1 levels in trametinib resistant cells, providing an explanation for the synergy that was observed. Combining MEKi with pan-RAFi may provide a promising treatment strategy for LGSOC patients, which warrants further clinical validation.
    Journal
    |
    MAP2K1 (Mitogen-activated protein kinase kinase 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • HES1 • MAML2 (Mastermind Like Transcriptional Coactivator 2)
    |
    Mekinist (trametinib)
    over1year
    IDH1 IN INTRAHEPATIC CHOLANGIOCARCINOMA: A COMPARATIVE GENOMIC ANALYSIS AND CLINICAL IMPACT (ILCA 2022)
    We highlighted several molecular differences with distinct prognostic implications between IDH1m and IDH1wt patients.
    Clinical • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • MTAP (Methylthioadenosine Phosphorylase) • PBRM1 (Polybromo 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH2 (Notch 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component)
    |
    TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • IDH1 mutation • ATM mutation • FGFR2 mutation • CDKN2A mutation • PBRM1 mutation • CDKN2B mutation • IDH wild-type • MTAP mutation • NBN mutation
    |
    FoundationOne® CDx
    over1year
    Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer. (PubMed, Front Immunol)
    This research is the first to emphasize the close relationship between distinct cell death modalities and the diversity and complexity of immune infiltration in TME. We established the CD_Score, which could help enhance our cognition of TME features and facilitate the clinical application of immunotherapy.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    TP53 mutation
    almost2years
    Differential expression profiles of immunoregulatory genes in poorly-differentiated and anaplastic thyroid carcinomas progressive from papillary carcinoma (ECP 2022)
    PDC and AC possess specific and different expression profiles of immunoregulatory genes even in the presence of a similar histological pattern of progression. Unexpectedly, progression of PC to AC is not associated with a wide deregulation of immunoregulatory mechanisms. However, a subset of genes is consistently impaired during AC progression, whose role as biomarkers and functional mechanisms need to be assessed and validated in future studies.
    EPCAM (Epithelial cell adhesion molecule) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RIPK2 (Receptor Interacting Serine/Threonine Kinase 2) • BLNK (B Cell Linker) • ITGA5 (Integrin Subunit Alpha 5) • ITGB1 (Integrin Subunit Beta 1)
    |
    nCounter® PanCancer Immune Profiling Panel
    almost2years
    Preoperative serum ctDNA predicts early hepatocellular carcinoma recurrence and response to systemic therapies. (PubMed, Hepatol Int)
    Preoperative serum ctDNA can be a practical noninvasive approach to predict recurrence after surgery and response to systemic therapies. ctDNA-guided HCC management should be recommended.
    Journal • IO biomarker • Circulating tumor DNA
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • LRP1B (LDL Receptor Related Protein 1B) • FAT1 (FAT atypical cadherin 1) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    Lenvima (lenvatinib)
    almost2years
    P-Rex1 Signaling Hub in Lower Grade Glioma Patients, Found by In Silico Data Mining, Correlates With Reduced Survival and Augmented Immune Tumor Microenvironment. (PubMed, Front Oncol)
    This PREX1 signaling hub signature correlated with increased risk of shorter survival of LGG patients from independent datasets and coincided with immune and endothelial transcriptomic signatures, indicating that myeloid infiltration and tumor angiogenesis might contribute to worsen brain tumor pathology. In conclusion, P-Rex1 and its putative signaling partners in LGG are indicative of a signaling landscape of the tumor microenvironment that correlates with poor prognosis and might guide the characterization of signaling targets leading the eventual development of immunotherapeutic strategies.
    Journal • IO biomarker
    |
    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22) • RPS6KA3 (Ribosomal Protein S6 Kinase A3) • FZD6 (Frizzled Class Receptor 6) • MAP2K3 (Mitogen-Activated Protein Kinase Kinase 3)
    almost2years
    Epifriedelinol Ameliorates DMBA-induced Breast Cancer in Albino Rats by Regulating the PI3K/AKT Pathway. (PubMed, Tohoku J Exp Med)
    No abstract available
    Preclinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    almost2years
    Comprehensive Characterization of a Novel E3-Related Gene Signature With Implications in Prognosis and Immunotherapy of Low-Grade Gliomas. (PubMed, Front Genet)
    Positive correlations between the risk signature and the tumor microenvironment immune cell infiltration and immune checkpoint molecules were also observed, implying that patients with the high-risk score may have better responses to immunotherapy. Overall, our findings might provide potential diagnostic and prognostic markers for LGG patients and offer meaningful insight for individualized treatment.
    Journal • Gene Signature • IO biomarker
    |
    AURKA (Aurora kinase A) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • TLE3 (TLE Family Member 3, Transcriptional Corepressor)
    almost2years
    High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing. (PubMed, NPJ Breast Cancer)
    Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low-level subclonal (in 10-10 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients.
    Journal • Tumor Mutational Burden
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • NCOR1 (Nuclear Receptor Corepressor 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    almost2years
    Molecular Analysis of Luminal Androgen Receptor Reveals Activated Pathways and Potential Therapeutic Targets in Breast Cancer. (PubMed, Cancer Genomics Proteomics)
    Our findings confirm a role for PI3K/AKT/mTOR signaling in the pathogenesis of LAR breast cancers and indicate that targeting this pathway, along with ERBB2 mutations, may represent an additional therapeutic strategy which deserves further exploration in larger studies.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TSC2 (TSC complex subunit 2) • RANBP2 (RAN Binding Protein 2) • EP300 (E1A binding protein p300) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
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    HER-2 mutation • AR expression
    almost2years
    MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy. (PubMed, J Clin Lab Anal)
    Overall, miR-203a-3p inhibits the oncogenic characteristics of TPC-1 and KTC-1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • BECN1 (Beclin 1) • MIR203A (MicroRNA 203a)
    almost2years
    Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population. (PubMed, Biol Res)
    Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SF3B1 (Splicing Factor 3b Subunit 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    almost2years
    The MAP3K1/c-JUN signaling axis regulates glioblastoma stem cell invasion and tumor progression. (PubMed, Biochem Biophys Res Commun)
    Furthermore, the c-JUN inhibitor JNK-IN-8 significantly decreased GSC invasion, proliferation, and stemness. Taken together, our study demonstrates that MAP3K1 regulates GSC invasion and tumor progression via activation of c-JUN signaling and indicates that the MAP3K1/c-JUN signaling axis is a therapeutic target for infiltrative GBM.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • JUN (Jun proto-oncogene)
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    JNK-IN-8
    almost2years
    Circ_0085315 promotes cell proliferation, invasion, and migration in colon cancer through miR-1200/MAP3K1 signaling pathway. (PubMed, Cell Cycle)
    circRNA_0085315 increased the phosphorylation levels of JNK, p38, and ERK1/2 by stimulating MAP3K1 up-regulation caused by miR-1200 inhibition. In conclusion, circRNA_0085315 serves as a ceRNA and promotes CC progression through the activation of the MAPK signaling pathway mediated via the miR-1200/MAP3K1 axis, suggesting that circRNA_0085315 may be a promising diagnostic and therapeutic target for CC.
    Journal
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    CDH1 (Cadherin 1) • MMP2 (Matrix metallopeptidase 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • CDH2 (Cadherin 2)
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    CDH1 expression
    2years
    Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer. (PubMed, Neoplasia)
    This shift in localization was associated with decreased proliferation, migration, and invasion. Our results suggest that small molecules that inhibit nuclear CRTC2 and p38 activity may provide therapeutic benefit to patients with HPV(+) HNSCC.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    2years
    Small-molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth. (PubMed, Proc Natl Acad Sci U S A)
    This leads to reduced tumor growth and reduced metastasis in pancreatic cancer models. Therefore, drug candidates like 39-100, that are IKKβ activation modulators, can be developed to treat pancreatic cancer.
    Journal
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    MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    2years
    Alpelisib (ALP) + fulvestrant (FUL) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Biomarker (BM) analyses by next-generation sequencing (NGS) from the SOLAR-1 study. (ASCO 2022)
    The unique mut profile of PIK3CA-alt tumors did not affect ALP + FUL benefit in pts with HR+, HER2– ABC. Clinical benefit was maintained regardless of alterations in most BMs, including ESR1 and genes implicated in CDK4/6i resistance, consistent with ALP targeting the PIK3CA driver oncogene.
    Clinical • Tumor mutational burden • Next-generation sequencing
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • FGFR1 (Fibroblast growth factor receptor 1) • ARID1A (AT-rich interaction domain 1A) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RAD21 (RAD21 Cohesin Complex Component)
    |
    HR positive • HER-2 negative • PIK3CA mutation
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    FoundationOne® CDx
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    Piqray (alpelisib) • fulvestrant
    2years
    Apolipoprotein B mRNA-Editing Catalytic Polypeptide-Like-Induced Protein Changes in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Throughout Disease Progression. (PubMed, JCO Precis Oncol)
    Our results show that APOBEC mutagenesis recurrently targets various known drivers of BC initiation, progression, and endocrine resistance.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • ZFHX3 (Zinc Finger Homeobox 3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • APOB (Apolipoprotein B)
    |
    TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • PIK3CA E545K • PIK3CA E542K • EGFR positive • APOBEC mutagenesis • PIK3CA E545 • PIK3CA E542
    2years
    Characteristic profile of blood-based ctDNA suggests angiogenesis and immune escape in hepatocellular carcinoma (AACR 2022)
    The results showed the mutation characteristic of tissues and ctDNA in HCC, and suggest that angiogenic and tumor immune escape related ctDNA-specific genes might be able to predict recurrence risk independently of baseline tissue samples.
    Circulating tumor DNA
    |
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • LRP1B (LDL Receptor Related Protein 1B) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    TP53 mutation • NOTCH1 expression