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    GENE:

    PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

    i
    Other names: PPP2R2A, Protein Phosphatase 2 Regulatory Subunit B Alpha, Serine/Threonine-Protein Phosphatase 2A 55 KDa Regulatory, Subunit B Alpha Isoform, PP2A Subunit B Isoform Alpha, Protein Phosphatase 2 (Formerly 2A), Regulatory Subunit B (PR 52), Alpha Isoform, PP2A Subunit B Isoform PR55-Alpha, PP2A Subunit B Isoform B55-Alpha, PP2A Subunit B Isoform R2-Alpha, PR55alpha, B55ALPHA, PR52A, PR55A
    5d
    PARPi-PANC: Niraparib as First Line Therapy With Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, Centre Leon Berard | Withdrawn --> Terminated; Study not feasible, patient accrual rate too low.
    Trial termination
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
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    Zejula (niraparib)
    13d
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    27d
    Alterations in the transcriptional profile of genes in tumors as a prerequisite for personalization of treatment in breast cancer patients (PubMed, Arkh Patol)
    Comparative mRNA expression analysis confirms that a short preoperative course of aromatase inhibitors induces a more potent and uniform molecular response, characterized by profound suppression of proliferation and complete inhibition of estrogen-dependent signaling. Tamoxifen therapy is also effective but results in less pronounced suppression of key targets and, crucially, may be accompanied by early activation of the MYC oncogene, a potential marker for resistance development.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • FGFR4 (Fibroblast growth factor receptor 4) • BIRC5 (Baculoviral IAP repeat containing 5) • TYMS (Thymidylate Synthetase) • AURKA (Aurora kinase A) • FOXA1 (Forkhead Box A1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • PTTG1 (PTTG1 Regulator Of Sister Chromatid Separation, Securin) • BAG1 (BAG Cochaperone 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • GATA3 (GATA binding protein 3) • KRT5 (Keratin 5) • MMP11 (Matrix Metallopeptidase 11) • MYBL2 (MYB Proto-Oncogene Like 2) • SFRP1 (Secreted frizzled related protein 1) • TMEM45B (Transmembrane Protein 45B) • ANLN (Anillin Actin Binding Protein) • CCNB1 (Cyclin B1) • SCGB2A2 (Secretoglobin Family 2A Member 2) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 negative • HER-2 expression
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    tamoxifen • letrozole • anastrozole
    1m
    Predicting bevacizumab efficacy: the emerging role of ACTL6B in colorectal cancer. (PubMed, J Gastrointest Oncol)
    A three-gene logistic model (ACTL6Blow/S1PR3high/PPP2R2Blow) yielded an AUC of 0.84 (95% CI: 0.79-0.89) for progressive disease under bevacizumab. ACTL6B, alone or combined with S1PR3 and PPP2R2B, constitutes a robust biomarker panel for stratifying CRC patients likely to benefit from bevacizumab, warranting prospective clinical qualification.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CD4 (CD4 Molecule) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • PPP2R2B (Protein Phosphatase 2 Regulatory Subunit Bbeta)
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    Avastin (bevacizumab)
    2ms
    PPP2R2A insufficiency enhances PD-L1 immune checkpoint blockade efficacy in lung cancer through cGAS-STING activation. (PubMed, J Clin Invest)
    Patients with NSCLC with a low PPP2R2A/PD-L1 ratio respond better to immune checkpoint blockade (ICB). These findings underscore the therapeutic potential of ICB in treating PPP2R2A-deficient NSCLC while suggesting that PPP2R2A deficiency could serve as a biomarker for guiding ICB-based therapies.
    Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • IFNAR1 (Interferon (alpha, beta and omega) receptor 1)
    3ms
    MASTL Promotes Hepatocellular Carcinoma Progression and Paclitaxel Resistance Through Mitotic Catastrophe. (PubMed, Cancer Sci)
    These findings establish MASTL as a critical oncogene in HCC through the E2F1-MASTL-PP2A-B55α axis, suggesting its potential as both a prognostic biomarker and therapeutic target for HCC. Future studies should explore MASTL inhibitors in combination with conventional chemotherapy to overcome drug resistance in HCC patients.
    Journal
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    PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • E2F1 (E2F transcription factor 1)
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    paclitaxel
    4ms
    miR-106b-5p as a Central Regulator of Cancer Progression and Chemotherapy-Induced Cardiotoxicity: From Molecular Mechanisms to Clinical Translation. (PubMed, Int J Mol Sci)
    Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity...Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure.
    Review • Journal
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    PTEN (Phosphatase and tensin homolog) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • TGFB1 (Transforming Growth Factor Beta 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • SMAD7 (SMAD Family Member 7) • HDAC4 (Histone Deacetylase 4) • MIR106B (MicroRNA 106b) • YY1 (YY1 Transcription Factor)
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    doxorubicin hydrochloride
    4ms
    Olaparib for patients with tumors harboring alterations in homologous recombination repair genes: Results from the drug rediscovery protocol. (PubMed, Int J Cancer)
    In conclusion, PARPi sensitivity varies across HRR-genes, indicating that relying solely on an altered common mechanistic pathway is insufficient to predict response. Future studies should target specific HRR-genes to assess subgroup-specific benefits and determine proper use of molecular diagnostics.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • CHEK1 (Checkpoint kinase 1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    Lynparza (olaparib)
    6ms
    The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells. (PubMed, Nat Commun)
    Additionally, we establish that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics.
    Journal
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    PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • CDK1 (Cyclin-dependent kinase 1)
    7ms
    Pathogenic Genomic Alterations in Circulating Tumor DNA Predict Overall Survival in Men with Metastatic Castrate-resistant Prostate Cancer. (PubMed, Eur Urol)
    Incorporation of PGAs from ctDNA into a CG model improved OS prediction by nearly 30% over a clinical model. This model can classify patients into risk groups and is useful for selecting patients in future mCRPC trials.
    Journal • Circulating tumor DNA
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    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • MSH6 (MutS homolog 6) • FANCA (FA Complementation Group A) • ZFHX3 (Zinc Finger Homeobox 3) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • RSPO2 (R-Spondin 2) • ZBTB16 (Zinc Finger And BTB Domain Containing 16) • NKX3-1 (NK3 homeobox 1)
    7ms
    A novel defined manganese metabolism-related gene signature for predicting the prognosis of pancreatic ductal adenocarcinoma. (PubMed, Oncol Lett)
    The results of the present study further elucidated the molecular processes underlying PDAC and highlight the crucial importance of manganese metabolism in its development. These biomarkers may provide significant prognostic insights and facilitate the advancement of targeted therapeutic strategies for PDAC.
    Journal • Gene Signature
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    MET (MET proto-oncogene, receptor tyrosine kinase) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • ATP1B1 (ATPase Na+/K+ transporting subunit beta 1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • KRT19 (Keratin 19) • IL1RAP (Interleukin 1 Receptor Accessory Protein) • CYP27A1 (Cytochrome P450 Family 27 Subfamily A Member 1) • KYNU (Kynureninase)
    8ms
    Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Yonsei University | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Checkpoint inhibition
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    HER-2 positive • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel