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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
    2ms
    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: Sep 2024 --> Oct 2025
    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 • HER-2 negative + ER positive
    |
    docetaxel • AZD8186
    9ms
    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
    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=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
    over1year
    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
    over1year
    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
    almost2years
    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
    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) | 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
    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, 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
    3years
    [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
    3years
    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
    over3years
    [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)
    over3years
    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
    over4years
    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)