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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
    2d
    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)
    7d
    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)
    7d
    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)
    7d
    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
    8d
    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
    11d
    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
    14d
    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
    14d
    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
    15d
    Debio 0123-106: A phase 1 trial to study how safe and tolerable Lunresertib is, alone or in Combination with RP-3500 or Debio 0123, whennadministered in patients with certain types of cancer (2023-510063-35-00)
    P1, N=63, Recruiting, Debiopharm International S.A. | N=38 --> 63
    Enrollment change
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    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MUC16 (Mucin 16, Cell Surface Associated)
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    TP53 mutation
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    lunresertib (Debio2513) • camonsertib (RP-3500) • zedoresertib (Debio 0123)
    15d
    Associations between molecular classification and response to intra-uterine levonorgestrel device therapy in patients with medically managed endometrial cancer and endometrial intra-epithelial neoplasia: a multi-center Endometrial Cancer Molecularly Targeted Therapy (ECMT2) Consortium study. (PubMed, Int J Gynecol Cancer)
    The complete response to levonorgestrel intra-uterine device therapy was lower than expected for endometrial intra-epithelial neoplasia. Response rates varied by molecular classification, with worse outcomes observed in deficient mismatch repair and p53 abnormal sub-types. Although limited by sample size, these findings suggest that levonorgestrel intra-uterine device therapy may not be sufficient for all molecular sub-groups.
    Journal
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    TP53 (Tumor protein P53) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
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    MSI-H/dMMR • TP53 wild-type • POLE mutation
    15d
    A Phase I Study of JLM019 Injection (clinicaltrials.gov)
    P1, N=115, Recruiting, Jecho Biopharmaceuticals Co., Ltd.
    New P1 trial
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    MSI (Microsatellite instability) • JAK2 (Janus kinase 2) • POLE (DNA Polymerase Epsilon) • JAK1 (Janus Kinase 1) • POLD1 (DNA Polymerase Delta 1)
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    MSI-H/dMMR • POLE mutation • POLD1 mutation