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    BIOMARKER:

    RNF43 mutation

    i
    Other names: RNF43, Ring Finger Protein 43, RING-Type E3 Ubiquitin Transferase RNF43, E3 Ubiquitin-Protein Ligase RNF43, RING Finger Protein 43, EC 2.3.2.27, RNF124
    Entrez ID:
    54894
    Related biomarkers:
    Expression
    Mutation
    Others
    4d
    Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels. (PubMed, Oncogene)
    When representative variants are heterozygously introduced into endogenous ZNRF3, their impact on β-catenin signaling mirrors that of heterozygous knockout, suggesting that the supposed dominant-negative effect is non-existent. In other words, so-called "hyperactivating" ZNRF3/RNF43 mutations behave as classical loss-of-function mutations at endogenous levels.
    Journal
    |
    RNF43 (Ring Finger Protein 43) • RSPO1 (R-Spondin 1) • ZNRF3 (Zinc And Ring Finger 3)
    |
    RNF43 mutation
    15d
    Gender-Based Differences in the Efficacy of Anti-EGFR/BRAF/MEK Targeted Therapy in Patients with BRAF-Mutated Metastatic Colorectal Cancer. (PubMed, Semin Oncol)
    We confirmed a significant gender-based dimorphism in the efficacy of anti-EGFR/BRAF/MEK therapy in patients with advanced-CRC harboring BRAF mutations that warrant further investigation.
    Journal • Metastases
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • BRAF mutation • BRAF V600 • RNF43 mutation
    23d
    Co-occurring mutations identify prognostic subgroups of microsatellite stable colorectal cancer. (PubMed, Mol Cancer)
    We report a genome-wide evaluation of co-occurring mutations in MSS CRCs, and suggest that co-mutations can improve the prognostic stratification compared to single mutations alone.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • SOX9 (SRY-Box Transcription Factor 9) • TCF7L2 (Transcription Factor 7 Like 2)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • PIK3CA mutation • BRAF V600 • APC mutation • RNF43 mutation
    |
    MSK-IMPACT
    1m
    RNF43 and ZNRF3: Versatile regulators at the membrane and their role in cancer. (PubMed, Biochim Biophys Acta Rev Cancer)
    Additionally, we describe in detail how phosphorylation and ubiquitination may finetune RNF43 and ZNRF3 activity. We also address the variety of mutations observed in cancers and the mechanism through which they support tumor growth, and challenge the prevailing view that specific missense mutations in the R-spondin and RING domains may possess dominant-negative activity in contributing to tumor formation.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43) • RSPO1 (R-Spondin 1) • ZNRF3 (Zinc And Ring Finger 3)
    |
    RNF43 mutation
    1m
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
    |
    FoundationOne® CDx
    2ms
    Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer. (PubMed, Gastroenterol Rep (Oxf))
    Actionable gene fusions are more prevalent in MSI-H, RAS/BRAF wildtype, or RNF43-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.
    Journal • MSi-H Biomarker
    |
    BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RNF43 (Ring Finger Protein 43) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    MSI-H/dMMR • BRAF mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • BRAF wild-type • RAS mutation • RNF43 mutation • NTRK fusion
    2ms
    Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study. (PubMed, EBioMedicine)
    The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • RNF43 (Ring Finger Protein 43)
    |
    TP53 mutation • KRAS mutation • HRD • TP53 wild-type • RNF43 mutation
    |
    gemcitabine
    3ms
    A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands (clinicaltrials.gov)
    P1, N=185, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion
    |
    BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43)
    |
    BRAF mutation • RNF43 mutation
    |
    spartalizumab (PDR001) • WNT974
    3ms
    Prognostic determinants in cancer survival: a multidimensional evaluation of clinical and genetic factors across 10 cancer types in the participants of Genomics England's 100,000 Genomes Project. (PubMed, Discov Oncol)
    This study provides a comprehensive view of clinicopathological and genetic prognostic factors across different cancer types and draws attention to less commonly known factors which might help produce more precise prognosis and survival estimates. The results from this study contribute to the understanding of cancer disease and could be used by researchers to develop complex prognostic models, which in turn could help predict cancer prognosis more accurately and improve patient outcomes.
    Journal • Tumor mutational burden
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • RNF43 (Ring Finger Protein 43) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CDH1 (Cadherin 1) • FANCE (FA Complementation Group E) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • PTEN mutation • NF1 mutation • RNF43 mutation
    3ms
    TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases. (PubMed, Heliyon)
    Gene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43)
    |
    TP53 mutation • EGFR amplification • RNF43 mutation • TP53 amplification
    3ms
    Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration. (PubMed, Cancer Immunol Immunother)
    This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    RNF43 (Ring Finger Protein 43) • CSF1R (Colony stimulating factor 1 receptor) • ADGRB3 (Adhesion G Protein-Coupled Receptor B3)
    |
    RNF43 mutation
    |
    Imfinzi (durvalumab) • gemcitabine
    6ms
    RNF43-mutations are associated with stronger antitumour immune responses and improved outcomes in pancreatic cancer (ECP 2024)
    RNF43mut cases show improved clinical outcomes and stronger antitumour immune responses than RNF43wt cases in MSSPDACs. Moreover, RNF43-mutations were significantly more frequent in MSI-PDACs. Our results underscore the need for deeper understanding of molecular factors modulating the biological behaviour and treatment response of PDACs that can help refining the stratification and optimizing the clinical management of patients.
    Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • RNF43 (Ring Finger Protein 43) • CD163 (CD163 Molecule) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule)
    |
    TMB-H • RNF43 mutation
    |
    Oncomine Tumor Mutation Load Assay
    7ms
    Molecular characteristics of early-onset compared with late-onset colorectal cancer: A case controlled study. (PubMed, Int J Surg)
    This study revealed a significantly higher MSI-H distribution rate in early-onset colorectal cancer, and EOCRC exhibits a distinct mutational signature coupled with higher PD-L1 expression. These findings hold promise in guiding personalized therapeutic strategies for improved disease management in EOCRC patients.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • FAT1 (FAT atypical cadherin 1) • CASP8 (Caspase 8) • FANCI (FA Complementation Group I) • KMT2B (Lysine Methyltransferase 2B) • DPYD (Dihydropyrimidine Dehydrogenase)
    |
    PD-L1 expression • MSI-H/dMMR • ATM mutation • ARID1A mutation • PBRM1 mutation • RNF43 mutation • KMT2B mutation • FANCI mutation
    7ms
    Novel insights into tumorigenesis revealed by molecular analysis of Lynch syndrome cases with multiple colorectal tumors. (PubMed, Front Oncol)
    Somatic variants in APC and CTNNB1 were unique to each tumor. Frequent somatic RNF43 hot spot variants combined with SBS96 signature and increased tendency to DNA methylation may contribute to tumor multiplicity in LS.
    Journal
    |
    RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    RNF43 mutation
    7ms
    Clinical study assessing the preliminary efficacy and safety of RXC004, in Patients with Advanced Pancreatic Cancer that have Progressed following Therapy with Current Standard of Care (ACTRN12624000588594)
    P2, N=20, Not yet recruiting, Australian Genomic Cancer Medicine Centre Ltd t/a Omico
    New P2 trial • Metastases
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    zamaporvint (RXC004)
    8ms
    Somatic mutations that affect early genetic progression and immune microenvironment in gastric carcinoma. (PubMed, Pathol Res Pract)
    HRD showed a positive correlation with tumor mutational burden, which might serve as indirect evidence supporting the potential of HRD as a biomarker for GC. These findings highlighted GC's high heterogeneity and complexity and provided valuable insights into the somatic mutations that affect early genetic progression and immune microenvironment.
    Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • KMT2C (Lysine Methyltransferase 2C) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin) • FAT4 (FAT Atypical Cadherin 4) • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • CSMD3 (CUB And Sushi Multiple Domains 3) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1) • XIRP2 (Xin Actin Binding Repeat Containing 2) • ZFHX4 (Zinc Finger Homeobox 4)
    |
    MSI-H/dMMR • HRD • ARID1A mutation • RNF43 mutation • SMAD4 mutation
    8ms
    Selective epigenetic alterations in RNF43 in pancreatic exocrine cells from high-fat-diet-induced obese mice; implications for pancreatic cancer. (PubMed, BMC Res Notes)
    Results revealed no significant differences in methylation levels in loci between HFD- and normal-fat-diet (NFD)-fed mice, except for RNF43, a negative regulator of Wnt signaling, which showed hypermethylation in three loci. These findings indicate that, in mouse pancreatic exocrine cells, high-fat dietary obesity induced aberrant DNA methylation in RNF43 but not in other frequently mutated PC-related genes.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • KRAS mutation • RNF43 mutation
    8ms
    Recurrent mutations in tumor suppressor FBXW7 bypass Wnt/β-catenin addiction in cancer. (PubMed, Sci Adv)
    These FBXW7-mutant Wnt/β-catenin-independent tumors are susceptible to multi-cyclin-dependent kinase inhibition. An in-depth understanding of primary resistance to anti-Wnt/β-catenin therapies allows for more appropriate patient selection and use of alternative mechanism-based therapies.
    Journal
    |
    RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
    |
    FBXW7 mutation • RNF43 mutation
    9ms
    NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study. (PubMed, Hepatol Commun)
    In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.
    Retrospective data • Journal • Next-generation sequencing • Cytology
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • BRAF mutation • ATM mutation • RNF43 mutation • GNAS mutation
    9ms
    Ring Finger 43 Hot-spot Frameshift Mutation G659V in Colorectal Cancer Patients: Report from a Tertiary Cancer Care Hospital in North India. (PubMed, Int J Appl Basic Med Res)
    To the best of our knowledge, this is the first study from North India to show the involvement of RNF43 p.G659fs variant in CRC patients. The mutation correlated with MMR protein deficiency and seems to be conferring tumorigenicity independent of the Wnt pathway.
    Journal
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation • RNF43 G659fs
    10ms
    A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC) (clinicaltrials.gov)
    P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • AXIN1 (Axin 1) • ZNRF3 (Zinc And Ring Finger 3)
    |
    APC mutation • CTNNB1 mutation • RNF43 mutation
    |
    E7386
    10ms
    Mucin phenotype and genetic alterations in non-V600E BRAF-mutated colorectal cancer. (PubMed, Hum Pathol)
    Considering the differences in mucin phenotype and genetic alterations, different modes of tumorigenesis are assumed for CRC with BRAF V600E mutation and non-V600E mutations. These findings are important in understanding the biology and treatment strategies for BRAF-mutant CRC.
    Journal
    |
    BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • MME (Membrane Metalloendopeptidase) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6)
    |
    BRAF V600E • APC mutation • RNF43 mutation • MUC5AC expression
    10ms
    Association of RNF43 Genetic Alterations With BRAFV600E and MSIhigh in Colorectal Cancer. (PubMed, JCO Precis Oncol)
    Ongoing phase III clinical trials, such as BREAKWATER, should aim to incorporate broader genetic profiling to further validate the superior sensitivity of patients with RNF43-mutant, MSS BRAFV600E CRC to anti-EGFR-/BRAFi-based therapies.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation • BRAF V600E + MSI-H/dMMR
    10ms
    Neoplastic Progression in Macroscopic Precursor Lesions of the Pancreas. (PubMed, Arch Pathol Lab Med)
    The recurrent alterations described in cysts provide an opportunity for diagnosis using aspirated cyst fluid. Molecular characterization of IPMNs shows a striking spatial and mutational heterogeneity, challenging traditional models of neoplastic development and creating challenges to interpretation of cyst fluid sequencing results.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • GNAS (GNAS Complex Locus) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha) • PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta)
    |
    TP53 mutation • KRAS mutation • RNF43 mutation • GNAS mutation
    10ms
    New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis. (PubMed, In Vitro Cell Dev Biol Anim)
    RNF43 may simultaneously play different roles in classical multistep tumorigenesis, as both wild-type and mutant RNF43 suppress the p53 pathway. We hope that the knowledge obtained from further research in RNF43 will be applied to cancer treatment in the future despite the fully unclear function of RNF43.
    Review • Journal
    |
    RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    TP53 mutation • RNF43 mutation
    10ms
    Molecular and Clinical Characterization of Oncocytic Intraductal Papillary Neoplasms of the Pancreas (USCAP 2024)
    The presence of a PRKACA/B fusion appears to contribute to oncocytic morphology, but 71% of fusion-positive cases had mixed epithelial subtypes. Rare cases harbored concurrent fusion and driver mutation associated with IPMN. Though fusion-positive lesions were more commonly seen in the non-recurrence group, they also comprised >50% of cases with disease recurrence.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • GNAS (GNAS Complex Locus) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)
    |
    KRAS mutation • RNF43 mutation • SMAD4 deletion • GNAS mutation • KRAS deletion
    |
    OncoPanel™ Assay
    11ms
    Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma. (PubMed, BMC Med)
    MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS.
    Journal • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • ACVR2A (Activin A Receptor Type 2A)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • ARID1A mutation • PBRM1 mutation • RNF43 mutation • PD-L1 expression + MSI-H/dMMR
    11ms
    RNF43 Inactivation Enhances the B-RAF/MEK Signaling and Creates a Combinatory Therapeutic Target in Cancer Cells. (PubMed, Adv Sci (Weinh))
    MEK and WNT inhibitors synergistically suppress the growth of RNF43-mutated pancreatic cancer cells in vitro and in vivo. Collectively, the research reveals a novel mechanism by which RNF43 inhibits B-RAF/MEK signaling to suppress tumor growth and provide a new strategy for the treatment of RNF43-inactivated pancreatic cancer.
    Journal
    |
    BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    11ms
    Clinical and molecular characteristics of RNF43 mutations as promising prognostic biomarkers in colorectal cancer. (PubMed, Ther Adv Med Oncol)
    Moreover, we observed that pMMR/MSS patients with RNF43 R117fs mutation had a higher incidence of stage IV, ⩾2 metastatic sites, low TMB, and none of them received PD-1/PD-L1 inhibitor therapy. Our findings provide the first evidence that RNF43 mutations in NTD and the R117fs variant correlate with a poorer prognosis in CRC patients, providing strategies for Wnt-targeted therapy to improve clinical efficacy.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • TMB-H • MSI-H/dMMR • BRAF V600 • TMB-L • RNF43 mutation
    11ms
    KEYNOTE-E86: A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=45, Completed, Redx Pharma Plc | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    Keytruda (pembrolizumab) • Prolia (denosumab) • zamaporvint (RXC004)
    11ms
    Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review. (PubMed, Gut)
    Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • RNF43 (Ring Finger Protein 43) • CEACAM5 (CEA Cell Adhesion Molecule 5) • GNAS (GNAS Complex Locus)
    |
    RNF43 mutation • GNAS mutation
    1year
    Canonical Wnt signaling pathway (WSP) alterations in metastatic prostate cancer. (ASCO-GU 2024)
    WSP-act prostate cancer demonstrated a pronounced upregulation of ROR1 gene expression, underscoring its potential involvement in the crosstalk between the canonical and non-canonical Wnt signaling pathways. Additionally, the augmented levels of M2 macrophages in WSP-act tumors, combined with the reported role of ROR1 in tumor immunosuppression, suggests that ROR1 may contribute to immune evasion in WSP-act mPCa. Our findings may provide rationale for developing novel therapeutic strategies targeting Wnt-activated prostate cancers.
    MSi-H Biomarker • Metastases
    |
    RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • SPOP (Speckle Type BTB/POZ Protein) • RSPO2 (R-Spondin 2)
    |
    MSI-H/dMMR • ROR1 expression • RNF43 mutation • SPOP mutation • RNF43 G659fs • CTNNB1 expression
    |
    MI Tumor Seek™
    1year
    RNF43 mutation as a predictor of immunotherapeutic efficacy in colorectal cancer. (PubMed, Am J Cancer Res)
    Our results suggest that RNF43 mutation may correlate with better OS in CRC patients receiving PD-1/PD-L1 inhibitors. The exact mechanisms underlying RNF43 require further investigation.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • RNF43 (Ring Finger Protein 43) • TGFBR2 (Transforming Growth Factor Beta Receptor 2)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • RNF43 mutation
    1year
    LMTK3 gene expression and the molecular landscape of colorectal cancer (CRC). (ASCO-GI 2024)
    Our data show a strong association between LMTK3 gene expression and distinct molecular features and TME immune cell infiltration in CRC. These findings suggest that LMTK3 may be an important molecular factor that plays a role in determining the composition of the TME, thus targeting LMTK3 could represent a novel strategy in selected CRC subgroups.
    MSi-H Biomarker • IO biomarker
    |
    ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • CD4 (CD4 Molecule) • CDX2 (Caudal Type Homeobox 2) • AMER1 (APC Membrane Recruitment Protein 1)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • ATM mutation • ASXL1 mutation • APC mutation • RNF43 mutation • SMAD4 mutation • MLL mutation
    1year
    High-resolution transcriptional signature to predict survival benefit in colorectal cancer (CRC) treated with EGFR inhibitors (EGFRi) independent of RAS/BRAF mutation status or tumor sidedness. (ASCO-GI 2024)
    Sponsored by NCI, NCI Background: Cetuximab (CTX) and Panitumumab (PMB) therapies directed at EGFR have been restricted to left-sided CRC harboring wild-type KRAS (KRASWT), limiting their utility. Our data suggest that CTX-S may predict longer survival on EGFRi, surprisingly independent of RAS/BRAF mutation status as well as tumor sidedness. Patients with high CTX-S had increased prevalence of CMS2 and harbored more APC and TP53 mutations. A strong EGFRi biomarker would likely expand the utility of EGFRi to right-sided tumors and possibly to RASMUT tumors.
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • KRAS wild-type • BRAF wild-type • RAS mutation • RAS wild-type • APC mutation • RAS wild-type + BRAF wild-type • RNF43 mutation
    |
    MI Tumor Seek™
    |
    Erbitux (cetuximab) • Vectibix (panitumumab)
    1year
    The impact of Wnt pathway alterations including RNF43, GNAS, CTNNB1, and APC on prognosis and potential therapeutic vulnerability in pancreatic adenocarcinoma (PDAC). (ASCO-GI 2024)
    Hazard ratios and p-values were computed via Cox regression when comparing PFS within subsets that received either 1st line FOLFIRINOX (FFX) or 1st line gemcitabine/nab-paclitaxel (GA)... The presence of Wnt pathway alterations identifies a subgroup of advanced PDAC with improved PFS and OS. >
    MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • KRAS mutation • MSI-H/dMMR • PIK3CA mutation • APC mutation • RNF43 mutation
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    1year
    Identification and characterization of immunogenic neoantigens in colorectal cancer (CRC). (ASCO-GI 2024)
    This is one of the largest studies to investigate the landscape of immunogenic neoantigens in CRC. We were able to identify candidate recurrent peptides with high HLA binding affinity and an association with a positive TIS signature supporting the role of neoantigens as potential cancer immunotherapy targets.
    MSi-H Biomarker • IO biomarker
    |
    MSI (Microsatellite instability) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • APC (APC Regulator Of WNT Signaling Pathway) • MSH3 (MutS Homolog 3) • SOX9 (SRY-Box Transcription Factor 9)
    |
    MSI-H/dMMR • APC mutation • RNF43 mutation • MSH3 mutation
    1year
    High overall copy number variation burden by genome-wide methylation profiling holds negative prognostic value in surgically treated pancreatic ductal adenocarcinoma. (PubMed, Hum Pathol)
    Importantly, our approach, using data from genome-wide methylation profiling for analysis of overall CNV burden, can be performed on formalin-fixed and paraffin embedded PDAC tissues. Future studies should examine the prognostic value of overall CNV burden in unresectable PDAC.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • KDM6A (Lysine Demethylase 6A) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • KRAS mutation • RNF43 mutation
    1year
    DNA Mutational Profiling in Patients With Colorectal Cancer Treated With Standard of Care Reveals Differences in Outcome and Racial Distribution of Mutations. (PubMed, J Clin Oncol)
    These results can provide new tools to predict patient outcome and improve therapeutic decisions and trial participation in patient minorities. The molecular alterations identified in this study may direct biomarker-driven studies.
    Journal • MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • KRAS mutation • MSI-H/dMMR • BRAF wild-type • RAS mutation • APC mutation • RNF43 mutation
    |
    Avastin (bevacizumab) • Erbitux (cetuximab)
    1year
    Enhancing cholangiocarcinoma immunotherapy with adoptive T cells targeting HLA-restricted neoantigen peptides derived from driver gene mutations. (PubMed, Biomed Pharmacother)
    Moreover, HLA-A* 11:01-restricted T cells exhibited elevated levels of IFN-gamma, granulysin, and granzyme B, indicating their potent anti-tumor capabilities. These findings underscore the specificity and efficiency of HLA-A* 11:01-restricted T cells targeting KRAS, RNF43, TP53 mutated CCA cells, and offer valuable insights for developing immunotherapeutic strategies and therapeutic peptide-vaccines for CCA treatment.
    Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HLA-A (Major Histocompatibility Complex, Class I, A) • IFNG (Interferon, gamma) • RNF43 (Ring Finger Protein 43) • GZMB (Granzyme B) • CD40 (CD40 Molecule) • ITGAX (Integrin Subunit Alpha X) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
    |
    TP53 mutation • KRAS mutation • RNF43 mutation • HLA-A*11
    1year
    Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer. (PubMed, JCO Precis Oncol)
    In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
    Journal • BRCA Biomarker • MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • SF3B1 (Splicing Factor 3b Subunit 1) • PALB2 (Partner and localizer of BRCA2) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • HLA-DPA1 (Major Histocompatibility Complex, Class II, DP Alpha 1)
    |
    TP53 mutation • BRCA2 mutation • MSI-H/dMMR • PALB2 mutation • KRAS wild-type • RAS wild-type • CDKN2A mutation • MET mutation • NRG1 fusion • BRAF fusion • RNF43 mutation • MET fusion
    1year
    Predictive Impact of RNF43 Mutations in Patients With Proficient Mismatch Repair/Microsatellite Stable BRAFV600E-Mutated Metastatic Colorectal Cancer Treated With Target Therapy or Chemotherapy. (PubMed, JCO Precis Oncol)
    Patients with pMMR/MSS BRAFV600E-mut mCRC achieve benefit from TT versus CT independently of RNF43 mutational status, although a higher magnitude of benefit from TT is observed in RNF43-mut tumors. These findings deserve confirmation in concluded and ongoing randomized trials.
    Journal • Mismatch repair • Metastases
    |
    RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • BRAF V600 • RNF43 mutation
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • oxaliplatin • irinotecan