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    BIOMARKER:

    PIK3CB mutation

    i
    Other names: PIK3CB, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta, Phosphatidylinositol 4,5-Bisphosphate 3-Kinase 110 KDa Catalytic Subunit Beta, Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta Isoform, Phosphoinositide-3-Kinase, Catalytic, Beta Polypeptide, PtdIns-3-Kinase Subunit P110-Beta, PtdIns-3-Kinase Subunit Beta, PI3-Kinase Subunit Beta, PI3K-Beta, PIK3C1, PI3-Kinase P110 Subunit Beta, PtdIns-3-Kinase P110, P110BETA, PI3KBETA, PI3Kbeta, P110beta
    Entrez ID:
    5291
    Related biomarkers:
    Expression
    Mutation
    CNA
    1m
    Establishment of a human ovarian clear cell carcinoma cell line mutant in PIK3CB but not PIK3CA. (PubMed, Hum Cell)
    Moreover, characteristic point mutations-one in ARID1A, which encodes the AT-rich interaction domain containing protein 1A, and the other in PIK3CB, which encodes the catalytic subunit of phosphoinositide 3-kinase-were seen in the patient's tumour tissue and retained in MTC-22 cells. Collectively, these findings indicate that MTC-22 cells could serve as a valuable tool for investigating the pathophysiology of ovarian clear cell carcinoma, particularly that harbouring PIK3CB mutations, and for developing and validating new diagnostic and therapeutic approaches to this life-threatening malignancy.
    Preclinical • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    PIK3CA mutation • ARID1A mutation • PIK3CB mutation
    7ms
    PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Sep 2024
    Trial completion date • Combination therapy • Surgery • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    ER positive • HR positive • HER-2 negative • ER positive + HER-2 negative • PIK3CB mutation
    |
    docetaxel • AZD8186
    1year
    AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20). (PubMed, Oncologist)
    Although the combination of AZD8186 and paclitaxel was well tolerated, limited clinical efficacy was observed.ClinicalTrials.gov Identifier: NCT04001569.
    P1/2 data • Journal • Combination therapy • Metastases
    |
    PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    PIK3CB mutation
    |
    paclitaxel • AZD8186
    1year
    PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=21, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 21 | Trial completion date: Apr 2023 --> Mar 2024 | Trial primary completion date: Apr 2023 --> Jul 2022
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Surgery • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    ER positive • HR positive • HER-2 negative • ER positive + HER-2 negative • PIK3CB mutation
    |
    docetaxel • AZD8186
    over1year
    Molecular Diversity of Testicular Embryonic-Type Neuroectodermal Tumors (ENT; former PNET) Arising from Germ Cell Tumors (USCAP 2023)
    PNETs arising from GCT are molecularly heterogeneous; however, a subset may be stratified by alterations in 1) MYCN/MYC/TP53/MDM2, 2) PIK3 pathways or 3) fusions that overlap with molecularly defined CNS-PNETs entities. Additional studies examining the prognostic and therapeutic implications of our findings are warranted.
    Tumor mutational burden
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MDM2 (E3 ubiquitin protein ligase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • EWSR1 (EWS RNA Binding Protein 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • CCND2 (Cyclin D2) • BRD4 (Bromodomain Containing 4) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
    |
    TP53 mutation • PIK3CA mutation • TMB-L • MDM2 amplification • CDK4 amplification • MDM2 mutation • PIK3CB mutation • PIK3CG mutation
    2years
    PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=58, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2022 --> Apr 2023 | Trial primary completion date: Apr 2022 --> Apr 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    ER positive • HR positive • HER-2 negative • ER positive + HER-2 negative • PIK3CB mutation
    |
    docetaxel • AZD8186
    over2years
    PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=58, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    ER positive • HR positive • HER-2 negative • ER positive + HER-2 negative • PIK3CB mutation
    |
    docetaxel • AZD8186
    over2years
    [VIRTUAL] Gene Expression and Mutation Analysis of Early-Stage Recurrent Endometrial Cancer (ASTRO 2021)
    Of recurrent early-stage tumors within the TCGA-UCEC dataset, of which as least a majority classify as intermediate or unfavorable according to PORTEC-4a criteria, differential gene expression in recurrent tumors compared to not recurrent tumors demonstrate relative increased expression of genes involved in catabolic and cell cycle processes. PORTEC-4a does not employ gene expression signatures to distinguish amongst favorable, intermediate, and unfavorable subtypes of early-stage endometrial tumors. However, further investigation may prove gene expression incorporation into stratification beneficial.
    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • DDIT3 (DNA-damage-inducible transcript 3) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    TP53 mutation • POLE mutation • CTNNB1 mutation • PIK3R1 mutation • PIK3CB mutation
    over2years
    Gene Expression and Mutation Analysis of Early-Stage Recurrent Endometrial Cancer. (PubMed, Int J Radiat Oncol Biol Phys)
    Of recurrent early-stage tumors within the TCGA-UCEC dataset, of which as least a majority classify as intermediate or unfavorable according to PORTEC-4a criteria, differential gene expression in recurrent tumors compared to not recurrent tumors demonstrate relative increased expression of genes involved in catabolic and cell cycle processes. PORTEC-4a does not employ gene expression signatures to distinguish amongst favorable, intermediate, and unfavorable subtypes of early-stage endometrial tumors. However, further investigation may prove gene expression incorporation into stratification beneficial.
    Journal
    |
    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • DDIT3 (DNA-damage-inducible transcript 3) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    TP53 mutation • POLE mutation • CTNNB1 mutation • PIK3R1 mutation • PIK3CB mutation
    3years
    [VIRTUAL] Clinical activity and safety of the RET inhibitor pralsetinib in patients with RET fusion-positive solid tumors: Update from the ARROW trial. (ASCO 2021)
    Pralsetinib showed robust, durable antitumor activity in patients with multiple RET fusion‒positive, heavily pre-treated, advanced solid tumors, and was well tolerated . These data highlight the need for broad RET testing to identify candidates who could benefit from treatment with pralsetinib . Enrollment of patients with other RET fusion–positive solid tumors in ARROW is ongoing.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • RET (Ret Proto-Oncogene) • KIF5B (Kinesin Family Member 5B) • CCDC6 (Coiled-Coil Domain Containing 6) • NCOA4 (Nuclear Receptor Coactivator 4) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    KRAS mutation • RET fusion • NCOA4-RET fusion • PIK3CB mutation • RET positive
    |
    Gavreto (pralsetinib)
    3years
    PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=58, Recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2021 --> Apr 2022 | Trial primary completion date: Apr 2021 --> Apr 2022
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    ER positive • HR positive • HER-2 negative • ER positive + HER-2 negative • PIK3CB mutation
    |
    docetaxel • AZD8186
    almost4years
    AZD8186 First Time In Patient Ascending Dose Study (clinicaltrials.gov)
    P1, N=147, Completed, AstraZeneca | Active, not recruiting --> Completed
    Clinical • Trial completion • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)
    |
    HER-2 negative • PIK3CB mutation
    |
    abiraterone acetate • AZD8186 • vistusertib (AZD2014)