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    GENE:

    POLD1 (DNA Polymerase Delta 1)

    i
    Other names: POLD1, DNA Polymerase Delta 1 Catalytic Subunit, Polymerase (DNA) Delta 1 Catalytic Subunit, DNA Polymerase Delta Catalytic Subunit, DNA Polymerase Subunit Delta P125, Polymerase (DNA Directed) Delta 1 Catalytic Subunit (125kD), Polymerase (DNA Directed) Delta 1 Catalytic Subunit 125kDa, CDC2 Homolog (S. Cerevisiae), CDC2 Homolog
    11d
    Hereditary Endometrial Cancer: Lynch Syndrome, Mismatch Repair Deficiency, and Emerging Genetic Predispositions-A Comprehensive Review with Clinical and Laboratory Guidelines. (PubMed, Int J Mol Sci)
    Despite major advances in molecular diagnostics, hereditary endometrial cancer remains frequently underdiagnosed, leading to missed opportunities for cancer prevention among affected individuals and their families. This comprehensive review summarises current evidence on hereditary predispositions to endometrial cancer, with a particular emphasis on Lynch syndrome, and discusses underlying genetic mechanisms, inheritance patterns, diagnostic strategies, and clinical implications for screening, genetic counselling, and treatment optimisation.
    Review • Journal • Mismatch repair • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • MSH6 (MutS homolog 6) • POLD1 (DNA Polymerase Delta 1)
    11d
    ZEB1 Promotes Alternate Lengthening of Telomeres at Multiple Levels. (PubMed, Cancers (Basel))
    These findings suggest a novel role for ZEB1 in promoting ALT both transcriptionally and post-transcriptionally at multiple levels.
    Journal
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    POLD1 (DNA Polymerase Delta 1) • WRN (WRN RecQ Like Helicase) • ESRP1 (Epithelial Splicing Regulatory Protein 1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1) • RPA3 (Replication Protein A3) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    15d
    The molecular profile of ovarian struma ovarii. (PubMed, Hum Pathol)
    Benign struma ovarii do not harbor BRAF alterations. DICER1 and POLD1 variants need further investigation in this tumor pathology.
    Journal
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    BRAF (B-raf proto-oncogene) • POLD1 (DNA Polymerase Delta 1) • DICER1 (Dicer 1 Ribonuclease III)
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    BRAF mutation • POLD1 mutation
    17d
    LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)
    P=N/A, N=5909, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Initiation date: Jun 2025 --> Feb 2026
    Trial initiation date
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • RAD51D (RAD51 paralog D) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • DICER1 (Dicer 1 Ribonuclease III) • FLCN (Folliculin) • PRSS1 (Serine Protease 1) • SDHD (Succinate Dehydrogenase Complex Subunit D) • TXNIP (Thioredoxin Interacting Protein) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • HOXB13 (Homeobox B13)
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    TP53 mutation • PTEN deletion
    24d
    A phase II clinical trial of epalolitoporvorellimab (QL1706) in combination with fruquintinib for the treatment of immunocompetent pMMR/MSS metastatic colorectal cancer that has failed second- or higher lines of therapy. (ChiCTR2500112464)
    P2, N=18, Not yet recruiting, Harbin Medical University Affiliated Cancer Hospital; Harbin Medical University Affiliated Cancer Hospital
    New P2 trial
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    PD-L1 (Programmed death ligand 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • KMT2A (Lysine Methyltransferase 2A) • POLD1 (DNA Polymerase Delta 1)
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    ARID1A mutation
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    Fruzaqla (fruquintinib) • Qibeian (iparomlimab/tuvonralimab)
    25d
    Exceptional response to chemo-immunotherapy in a patient with HER2-negative, TMB-high metastatic gastric mucinous adenocarcinoma: a case report and literature review. (PubMed, Front Immunol)
    Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.
    Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • POLD1 (DNA Polymerase Delta 1)
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    TMB-H • HER-2 negative • POLD1 mutation
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    Opdivo (nivolumab) • capecitabine • oxaliplatin
    27d
    Molecular Classification and Clinical Outcomes in Endometrial Cancer: Real-World Evidence from a Tertiary Care Center. (PubMed, Cancers (Basel))
    MMR and p53 IHC serve as practical frontline tools, while POLE sequencing should be prioritized for intermediate- and high-risk endometrioid tumors. Expanded molecular testing in Asian populations is essential to refine risk stratification and optimize individualized management.
    Clinical data • Journal • HEOR • Real-world evidence
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    POLE (DNA Polymerase Epsilon) • POLD1 (DNA Polymerase Delta 1)
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    TP53 mutation • MSI-H/dMMR • POLE mutation • POLD1 mutation
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    Idylla™ POLE-POLD1 Mutation Assay
    28d
    Evolution of AR and non-AR alterations in circulating tumor DNA of metastatic prostate cancer patients treated in the phase 3 Alliance A031201 trial. (PubMed, Clin Cancer Res)
    AR alterations in ctDNA accumulate at progression in mCRPC patients treated with ARPIs, especially in those with initially durable responses. These findings support the use of liquid biopsy to serially track resistance mechanisms and inform precision therapy in advanced prostate cancer.
    P3 data • Journal • Circulating tumor DNA
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • ZNRF3 (Zinc And Ring Finger 3)
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    Xtandi (enzalutamide) • abiraterone acetate
    1m
    PEPN2112: Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Mar 2026
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • FOXO1 (Forkhead box O1) • XRCC2 (X-Ray Repair Cross Complementing 2) • ATF1 (Activating Transcription Factor 1) • PAX3 (Paired Box 3)
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    elimusertib (BAY 1895344)
    1m
    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, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date • 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 • FoundationOne® Liquid CDx
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    Lynparza (olaparib)
    2ms
    CRISPR-Cas9-Loaded Theranostic Liposomes for Enhancing Radiosensitization of Prostate Cancer through POLD4 Gene Editing under Real-Time MRI Monitoring. (PubMed, Adv Sci (Weinh))
    Notably, PIO@Lipo displayed superior MRI contrast enhancement capability and passive tumor targeting ability. In conclusion, this study has identified POLD4 as a potent target for radiosensitization, capable of disrupting DNA damage-repair homeostasis through MRI-monitored gene editing, thereby offering a promising strategy to enhance the efficacy of radiotherapy in prostate cancer.
    Journal
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    POLD1 (DNA Polymerase Delta 1)
    2ms
    Case Report: Expansion of the POLD1-related polymerase proofreading-associated polyposis spectrum: first report of duodenal adenocarcinomas and characterization of two likely pathogenic variants. (PubMed, Front Oncol)
    Our report expands both the phenotypic and molecular spectrum of POLD1-associated PPAP by documenting the first duodenal adenocarcinomas in germline carriers and describing a novel variant. These findings emphasize the need for systematic upper gastrointestinal surveillance, support the systematic reporting of rare POLD1 variants to refine genotype-phenotype correlations, and underline the potential therapeutic relevance of identifying carriers in the context of immunotherapy.
    Journal • Tumor mutational burden • IO biomarker
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    TMB (Tumor Mutational Burden) • POLD1 (DNA Polymerase Delta 1)
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    TMB-H