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    GENE:

    POLE (DNA Polymerase Epsilon)

    i
    Other names: POLE1, DNA Polymerase Epsilon Catalytic Subunit, DNA Polymerase Epsilon Catalytic Subunit A, Polymerase (DNA) Epsilon Catalytic Subunit, DNA Polymerase II Subunit A, Polymerase (DNA Directed) Epsilon Catalytic Subunit, DNA Polymerase Epsilon Catalytic Subunit Protein, Polymerase (DNA Directed) Epsilon
    5d
    NOMIC: Non-Operative Management and Following Immunotherapy for Colorectal Cancer and Other GI Cancers (clinicaltrials.gov)
    P=N/A, N=50, Not yet recruiting, Peking University Cancer Hospital & Institute
    New trial
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    MSI-H/dMMR • POLE mutation
    6d
    Morphological and molecular-genetic evolution of the endometrial polyp to adenocarcinoma (PubMed, Arkh Patol)
    At the same time, in the tissue of atypical hyperplasia and adenocarcinoma, this mutation led to an explosive accumulation of oncogenic genetic variants. This observation indicates role of mutation in the POLE gene as an early driver of carcinogenesis and emphasizes the importance of its determination in atypical endometrial proliferations.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
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    MSI-H/dMMR
    6d
    Navigating Immunotherapy in a Kidney Transplant Recipient: A Case Report of POLE-Mutated Jejunal Adenocarcinoma. (PubMed, Cureus)
    We present a renal transplant recipient with metastatic small bowel adenocarcinoma harboring a POLE mutation who was treated with pembrolizumab and achieved a complete metabolic response on PET-CT with negative circulating tumor DNA. This case suggests that immune checkpoint inhibitors may be considered in carefully selected transplant recipients with high tumor mutational burden, though risks remain.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon)
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    TMB-H • POLE mutation
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    Keytruda (pembrolizumab)
    6d
    Temozolomide, Cisplatin, and Nivolumab in People With Colorectal Cancer (clinicaltrials.gov)
    P2, N=18, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed
    Trial completion
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    BRAF (B-raf proto-oncogene) • POLE (DNA Polymerase Epsilon)
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    MSI-H/dMMR
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    Opdivo (nivolumab) • cisplatin • temozolomide
    8d
    Severe renal toxicity following adjuvant envafolimab in a patient with ultra-hypermutated (POLE) stage II colorectal cancer: a case report. (PubMed, AME Case Rep)
    For early-stage POLE-mutated CRC with favorable prognosis, off-label adjuvant immunotherapy may bring unnecessary toxicity risks. It is necessary to conduct rigorous patient selection, comprehensive risk-benefit evaluation, and close monitoring of organ function during treatment, so as to provide reference for the standardized clinical application of ICIs in this population.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • POLE (DNA Polymerase Epsilon)
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    BRAF V600E • KRAS mutation • TMB-H • BRAF V600 • POLE mutation
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    Enweida (envafolimab)
    13d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx
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    Lynparza (olaparib)
    13d
    POD1UM-204: Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy. (clinicaltrials.gov)
    P2, N=206, Completed, Incyte Corporation | Active, not recruiting --> Completed
    Trial completion
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    PD-L1 expression • MSI-H/dMMR • FGFR mutation
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    Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr) • epacadostat (INCB024360) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
    13d
    NOR-MP: Safety and Efficacy of NOM and OPFS Versus RO for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers (clinicaltrials.gov)
    P=N/A, N=22, Not yet recruiting, Peking University Cancer Hospital & Institute
    New trial • MSI-H • dMMR
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    MSI-H/dMMR
    14d
    SHAPE-ENDO: Pilot Randomized Trial of Multimodal Pre-Surgical Optimization Versus Standard Surgery in Patients With Obesity and Early-Stage Endometrial Cancer (clinicaltrials.gov)
    P4, N=80, Not yet recruiting, Hospital Universitari de Bellvitge | Trial completion date: Sep 2028 --> Jan 2035 | Initiation date: Sep 2026 --> Jan 2027 | Trial primary completion date: May 2027 --> Apr 2031
    Trial completion date • Trial initiation date • Trial primary completion date
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    ER (Estrogen receptor) • TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon)
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    TP53 mutation • ER positive • TP53 wild-type • POLE mutation
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    megestrol
    17d
    Microsatellite status and minimal microsatellite shift in atypical endometrial hyperplasia and endometrial cancer: an analysis of 848 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    Minimal microsatellite shift is commonly detected in MSI-H cases, and some cases are difficult to interpret due to their classification within the equivocal range. Increasing the number of microsatellite loci, combined with visualization graph comparison and integration of mismatch repair protein immunophenotype and histological features, can effectively improve the accuracy of MSI-H interpretation.
    Journal • MSi-H Biomarker
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • POLE mutation
    20d
    Molecular subtypes and lymph-node metastasis in endometrial cancer: An updated systematic review and meta-analysis. (PubMed, Surg Oncol)
    Molecular classification provides clinically meaningful information beyond traditional histopathologic factors and is closely associated with the risk of lymph-node metastasis in endometrial cancer. The consistently low nodal involvement observed in POLEmut and the high risk observed in p53abn support a more tailored approach to surgical staging.
    Retrospective data • Review • Journal
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    POLE (DNA Polymerase Epsilon)
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    TP53 mutation • MSI-H/dMMR • POLE mutation
    20d
    Rarity Within Rarity: Complete Response to Chemoimmunotherapy in a Patient with Polymerase epsilon (POLE)-Mutated locally advanced Jejunal Carcinoma. (PubMed, Oncologist)
    This case underscores the role of immunotherapy in POLE-mutated tumors regardless of the site of origin and highlights the potential usefulness of molecular profiling in rare malignancies. In line with the agnostic approach used for microsatellite instability, molecular-driven clinical trials should be prioritized over histology-based studies to optimize treatment strategies for these orphan diseases.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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    POLE mutation
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    Opdivo (nivolumab) • 5-fluorouracil • leucovorin calcium