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    GENE:

    POLD2 (DNA Polymerase Delta 2)

    i
    Other names: DNA Polymerase Delta 2 Accessory Subunit, DNA Polymerase Delta Subunit P50, Polymerase (DNA Directed) Delta 2 Regulatory Subunit 50kDa, Polymerase (DNA) Delta 2 Accessory Subunit, DNA Polymerase Delta Subunit 2, Pol Delta B Subunit (P50), Polymerase (DNA Directed) Delta 2 Regulatory Subunit (50kD), Polymerase (DNA Directed), Delta 2 Accessory Subunit, POLD2
    4ms
    Transcriptomic Profile of the Trastuzumab-Resistant Breast Cancer Cell Line BT-474 (PubMed, Mol Biol (Mosk))
    The changes identified indicate a complex reprogramming of transcriptional activity affecting cell cycle processes, DNA repair, metabolism, and the epithelial-mesenchymal transition. The findings expand our understanding of the molecular mechanisms of trastuzumab resistance and open prospects for the development of novel therapeutic strategies to overcome drug resistance in HER2-positive breast cancer.
    Preclinical • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • POLD1 (DNA Polymerase Delta 1) • POLD2 (DNA Polymerase Delta 2) • YBX1 (Y-Box Binding Protein 1) • E2F1 (E2F transcription factor 1) • FSTL1 (Follistatin Like 1) • HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1) • NFIC (Nuclear Factor I C) • TFAP2A (Transcription Factor AP-2 Alpha) • NCOA1 (Nuclear Receptor Coactivator 1)
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    HER-2 positive
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    Herceptin (trastuzumab)
    5ms
    BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies. (PubMed, bioRxiv)
    In particular, we proposed a synergistic combination of the BCL2 family inhibitor ABT-263 (Navitoclax) and the DNA analog TAS-102 (Lonsurf), which revealed that lysosomal modulation is a key mechanism driving DNA analog resistance. Together, these findings establish BOGO as a powerful gene overexpression perturbation platform for systematically identifying chemoresistance and chemosensitization drivers, and for discovering rational combination therapies. Its scalability and reproducibility position BOGO as a broadly applicable tool for functional genomics and therapeutic discovery beyond cancer resistance.
    Journal • IO biomarker
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    POLD1 (DNA Polymerase Delta 1) • POLD2 (DNA Polymerase Delta 2)
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    navitoclax (ABT 263) • Lonsurf (trifluridine/tipiracil)
    7ms
    Using machine learning to discover DNA metabolism biomarkers that direct prostate cancer treatment. (PubMed, Sci Rep)
    These genes not only serve as potential biomarkers for prognosis but also offer promising targets for personalized therapies. The integration of multi-omics data and advanced computational models provides new insights into the molecular underpinnings of PC and holds potential for improving treatment strategies.
    Journal
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    MSH6 (MutS homolog 6) • POLD1 (DNA Polymerase Delta 1) • POLD2 (DNA Polymerase Delta 2) • REV3L (REV3 Like DNA Directed Polymerase Zeta Catalytic Subunit) • RAD9A (RAD9 Checkpoint Clamp Component A)
    8ms
    Construction and validation of a prognostic model for glioma: an analysis based on mismatch repair-related genes and their correlation with clinicopathological features. (PubMed, Transl Cancer Res)
    In summary, our results indicate a marked elevation in EXO1 expression levels within gliomas, which correlates strongly with clinical pathological characteristics and unfavorable prognosis. Moreover, EXO1 emerges as a promising candidate biomarker and potential therapeutic target for glioma, likely playing a critical role in mediating immune infiltration within this malignancy.
    Journal • Mismatch repair
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    POLD1 (DNA Polymerase Delta 1) • POLD2 (DNA Polymerase Delta 2) • EXO1 (Exonuclease 1) • RFC4 (Replication Factor C Subunit 4) • RPA3 (Replication Protein A3)
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    IDH wild-type
    10ms
    The identification and prediction of lung adenocarcinoma prognosis using a novel gene signature associated with DNA replication. (PubMed, Transl Cancer Res)
    An innovative signature related to DNA replication was found to be a good prognostic predictor of LUAD. Our findings may provide novel insights into the diagnosis and treatment of LUAD.
    Journal • Gene Signature • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • PD-L2 (Programmed Cell Death 1 Ligand 2) • POLD1 (DNA Polymerase Delta 1) • PCNA (Proliferating cell nuclear antigen) • POLD2 (DNA Polymerase Delta 2) • MCM4 (Minichromosome Maintenance Complex Component 4) • POLE4 (DNA Polymerase Epsilon 4 Accessory Subunit) • SIGLEC15 (Sialic Acid Binding Ig Like Lectin 15) • FEN1 (Flap Structure-Specific Endonuclease 1) • MCM2 (Minichromosome maintenance complex component 2) • MCM5 (Minichromosome Maintenance Complex Component 5) • MCM7 (Minichromosome Maintenance Complex Component 7) • RPA3 (Replication Protein A3) • MCM6 (Minichromosome Maintenance Complex Component 6) • POLA2 (DNA Polymerase Alpha 2)
    11ms
    DNA Polymerase Delta 2 Activates Cell Cycle in Lung Adenocarcinoma, Leading to High Malignancy and Poor Prognosis. (PubMed, Ann Surg Oncol)
    We provide the possibility of POLD2 as a potential new therapeutic target because high POLD2 expression is associated with high malignancy and poor prognosis in specimens from patients with lung adenocarcinoma and POLD2 depletion triggers the suppression of cell migration, cell cycle progression, and cell proliferation.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • POLD1 (DNA Polymerase Delta 1) • POLD2 (DNA Polymerase Delta 2) • E2F1 (E2F transcription factor 1)
    over1year
    Deciphering the ghost proteome in ovarian cancer cells by deep proteogenomic characterization. (PubMed, Cell Death Dis)
    To identify the possible involvement of AltProts in cellular processes, cross-linking-MS (XL-MS) was performed in each cell line to identify AltProt-RefProt interactions. This approach revealed an interaction between POLD3 and the AltProt IP_183088, which after molecular docking, was placed between POLD3-POLD2 binding sites, highlighting its possibility of the involvement in DNA replication and repair.
    Journal
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    POLD2 (DNA Polymerase Delta 2) • POLD3 (DNA Polymerase Delta 3)
    over1year
    Development of the TP53 mutation associated hypopharyngeal squamous cell carcinoma prognostic model through bulk multi-omics sequencing and single-cell sequencing. (PubMed, Braz J Otorhinolaryngol)
    The prognostic model exhibited a significant capacity for predicting the prognosis of HSPCC samples based on the TP53 mutation conditions and may also predict the cancer characteristics and immune infiltration scores of samples via different risk scores obtained from the model.
    Journal
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    TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • POLD1 (DNA Polymerase Delta 1) • CD4 (CD4 Molecule) • POLD2 (DNA Polymerase Delta 2)
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    TP53 mutation
    almost2years
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Completed, Asan Medical Center | Active, not recruiting --> Completed
    Trial completion
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
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    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
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    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab-actl)
    almost3years
    PARP1 and POLD2 as prognostic biomarkers for multiple myeloma in autologous stem cell transplant. (PubMed, Haematologica)
    In pre-clinical models of MM, synergy was observed in anti-tumor activity when poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib, talazoparib) were used in combination with melphalan. The negative prognosis associated with PARP1 and POLD2 expression along with the apparent melphalan sensitizing effect of PARP inhibition may suggest this pathway as a potential biomarker in patients with MM in the setting of ASCT. Further understanding of the role of the BER pathway in MM is vital to improve therapeutic strategies related to ASCT.
    Journal • PARP Biomarker
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    POLD1 (DNA Polymerase Delta 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • POLD2 (DNA Polymerase Delta 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)
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    Lynparza (olaparib) • Talzenna (talazoparib) • melphalan
    3years
    GC 2nd Line Durvalumab(MEDI4736)/Tremelimumab Plus Paclitaxel Study (clinicaltrials.gov)
    P1/2, N=58, Active, not recruiting, Asan Medical Center | Unknown status --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2023 | Trial primary completion date: Jun 2021 --> Jun 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • POLD1 (DNA Polymerase Delta 1) • MSH3 (MutS Homolog 3) • PMS1 (PMS1 protein homolog 1) • POLD2 (DNA Polymerase Delta 2)
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    MSI-H/dMMR • MSH2 mutation • MLH1 mutation • PD-L1 amplification • POLD1 mutation • MSH3 mutation • PMS2 mutation • MLH3 mutation • PMS1 mutation • POLD2 mutation
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    Imfinzi (durvalumab) • paclitaxel • Imjudo (tremelimumab-actl)