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    BIOMARKER:

    PIK3CA H1047

    i
    Other names: PIK3CA, Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, Phosphoinositide-3-kinase, catalytic, alpha polypeptide, Serine/threonine protein kinase PIK3CA, PtdIns-3-kinase subunit P110-alpha, PI3K-alpha, Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 KDa catalytic subunit alpha, Phosphatidylinositol 3-kinase, Catalytic, 110-KD, alpha, PI3-kinase P110 subunit alpha, PI3-kinase subunit alpha, PtdIns-3-kinase subunit alpha, PI3Kalpha, P110alpha, PI3K
    Entrez ID:
    5290
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    9ms
    Comprehensive genomic profiling of advanced breast cancer subtypes: Insights from liquid biopsy analysis and implications for personalized therapies (AACR 2024)
    This study offers insights into the genomic landscape of advanced breast cancer subtypes through liquid biopsy. The observed prevalence of PIK3CA mutations supports the potential efficacy of PI3K inhibitors across these diverse types of breast cancer, laying the groundwork for personalized therapeutic strategies and biomarker identification for prognosis and targeted therapies.
    BRCA Biomarker • Liquid biopsy • Metastases • Biopsy
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR1 (Fibroblast growth factor receptor 1) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    HER-2 positive • TP53 mutation • HR positive • PIK3CA mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    PredicineCARE™
    11ms
    Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov)
    P1/2, N=102, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Checkpoint inhibition • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib) • ABP 206 (nivolumab biosimilar)
    11ms
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1, N=108, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    11ms
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1, N=108, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    12ms
    The genomic landscape of patients with advanced colorectal adenocarcinoma with PIK3CA mutations using comprehensive cell free tumor DNA next generation sequencing. (ASCO-GI 2024)
    Our study shows the frequency of PIK3CAm and distribution of exons 9 and 20 are similar to those found previously in the literature by Tan (Xie) et al., 2022. Our results demonstrate PIK3CA having a low frequency of MSI-H co-occurrence, higher TMB scores, and increased co-occurring alterations with notable increased in APC, BRAF, EGFR, ERBB2 and KRAS, which may suggest higher genomic instability. Our findings underscore the clinical significance of PIK3CAm in the context of CRC, emphasizing their role as key drivers of oncogenesis, and supports the development of tailored therapeutic strategies such as combining PIK3CAi with immunotherapy or other targeted therapies.
    Clinical • MSi-H Biomarker • IO biomarker • Next-generation sequencing • Circulating tumor DNA • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    BRAF V600E • KRAS mutation • TMB-H • MSI-H/dMMR • KRAS G12C • PIK3CA mutation • KRAS G12 • KRAS G13 • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA Q546
    |
    Guardant360® CDx
    almost1year
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1, N=108, Recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1
    Phase classification • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    1year
    Liquid Biopsy Testing in a Greek Cohort of ER-positive, HER2-negative metastatic breast cancer patients (SABCS 2023)
    CONCLUSION More than 20% of the ER-positive, HER2-negative breast cancer patients with metastatic disease are eligible for targeted treatment with elacestrant. In addition, the high prevalence of mutations detected in our cohort indicates that liquid biopsy NGS panel testing can be used to monitor treatment response, track the development of resistance, and identify emerging genetic alterations that may guide treatment adjustments or the selection of alternative targeted therapies in breast cancer patients.
    Clinical • Liquid biopsy • Metastases • Biopsy
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    TP53 mutation • KRAS mutation • ER positive • HER-2 negative • PIK3CA mutation • ESR1 mutation • PIK3CA H1047
    |
    Orserdu (elacestrant)
    over1year
    Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov)
    P1/2, N=102, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed • Checkpoint inhibition • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib) • ABP 206 (nivolumab biosimilar)
    over1year
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1b, N=108, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    almost2years
    Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov)
    P1/2, N=102, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023
    Trial completion date • Trial primary completion date • Checkpoint inhibition • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib)
    almost2years
    Prospective observational study of monitoring gene alterations in plasma cell-free DNA using droplet digital PCR system during anti-EGFR antibody treatment in patients with RAS wild-type advanced colorectal cancer. (ASCO-GI 2023)
    Our study demonstrated the clinical relevance of minor mutant subclones in EGFR signaling pathway genes in plasma for predicting response to anti-EGFR treatment. Although sample size of this study was small, preferable threshold for distinguishing responders from non-responders may be 0.5% as VAF of these gene mutations. Clinical trial information: 000034923.
    Clinical • Observational data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RAS (Rat Sarcoma Virus)
    |
    KRAS mutation • BRAF mutation • HER-2 amplification • NRAS mutation • PIK3CA mutation • BRAF V600 • MET amplification • RAS wild-type • MET mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61 • PIK3CA E545 • PIK3CA H1047 • NRAS A59
    almost2years
    Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations. (PubMed, JCO Precis Oncol)
    This analysis established that tumor PIK3CAmut prevalence can differ among predicted genetic ancestries across BC subtypes on the basis of the largest comprehensive genomic profiling data set of patients with cancer treated in the United States. This study highlights the need for equitable representation in research studies, which is imperative to ensuring better health outcomes for all.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    ER positive • HER-2 negative • PIK3CA mutation • EGFR positive • PIK3CA H1047
    2years
    STX-478, a mutant-selective PI3Kα H1047X inhibitor clinical candidate with a best-in-class profile: Pharmacology and therapeutic activity as monotherapy and in combination in breast cancer xenograft models (SABCS 2022)
    When combined with fulvestrant, lapatinib, or abemaciclib, STX-478 demonstrated synergistic anti-proliferative activity in cell lines with relevant ER/HER2 status...In the T47D (PI3Kα H1047R) breast cancer model, STX-478 (100 mg/kg) monotherapy caused tumor regression whereas alpelisib caused only stasis...In an ER+/HER2+ PDX model (PI3Kα H1047R/R108H), palbociclib and STX-478 (100 mg/kg) monotherapy resulted in similar efficacy while the combination was well tolerated and yielded tumor regression...The significant CNS exposure of STX-478 is expected to enable this treatment for patients with brain tumors and brain metastases not afforded by existing options. STX-478 is currently in IND enabling studies and is expected to enter human clinical trials in 2023.
    Preclinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA H1047
    |
    Ibrance (palbociclib) • lapatinib • Piqray (alpelisib) • Verzenio (abemaciclib) • fulvestrant • STX-478
    2years
    Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer (clinicaltrials.gov)
    P1/2, N=6, Terminated, David VanderWeele | Trial completion date: Dec 2024 --> Aug 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2022; Funder Decision
    Trial completion date • Trial termination • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    PIK3CA mutation • PTEN expression • AKT1 mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA Q546
    |
    ipatasertib (RG7440) • Nubeqa (darolutamide)
    2years
    Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer (clinicaltrials.gov)
    P1/2, N=6, Active, not recruiting, David VanderWeele | Recruiting --> Active, not recruiting | N=38 --> 6
    Enrollment closed • Enrollment change
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    PIK3CA mutation • PTEN expression • AKT1 mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA Q546
    |
    ipatasertib (RG7440) • Nubeqa (darolutamide)
    over2years
    Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer (clinicaltrials.gov)
    P1/2, N=38, Recruiting, David VanderWeele | Trial primary completion date: Feb 2022 --> Dec 2023
    Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    PIK3CA mutation • PTEN expression • AKT1 mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA Q546
    |
    ipatasertib (RG7440) • Nubeqa (darolutamide)
    over2years
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1b, N=102, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
    Trial completion date • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CD4 (CD4 Molecule) • 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) • XRCC2 (X-Ray Repair Cross Complementing 2)
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    over2years
    In vitro anticancer effects of alpelisib against PIK3CA‑mutated canine hemangiosarcoma cell lines. (PubMed, Oncol Rep)
    By contrast, it had no significant effect on canine mammary gland tumor cell lines harboring PIK3CA mutations. On the whole, the findings of the present study suggest that alpelisib may be highly effective against PIK3CA mutations that occur frequently in canine HSA.
    Preclinical • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation • PIK3CA H1047
    |
    Piqray (alpelisib)
    over2years
    Discovery and characterization of a mutant selective PI3KαH1047Xinhibitor with a best-in-class profile (AACR 2022)
    Alpelisib is a PI3Kα isoform-selective, orthosteric kinase inhibitor, having equivalent activity on wild-type (wt) and mutant (mt) forms and was approved to treat PI3Kα mt, HR+/HER2- breast cancer in combination with fulvestrant, nearly doubling progression-free survival (Andre 2019)...ST-814 has robust anti-tumor activity in PI3KαH1047X in xenografts, with efficacy similar or superior to alpelisib dosed at 50 mg/kg (Table 1)...A clinical candidate from this program is currently in IND enabling studies. >
    Late-breaking abstract
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA H1047X
    |
    Piqray (alpelisib) • fulvestrant • STX-478
    over3years
    Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)
    P1b, N=102, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CD4 (CD4 Molecule) • 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) • XRCC2 (X-Ray Repair Cross Complementing 2)
    |
    PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)
    over3years
    [VIRTUAL] A comprehensive characterization of hyper-morph, hypo-morph, and neo-morph mutations in cancer (AACR 2021)
    Further validation of these mutations using PIK3CA reporter assays led to the identification of several significant hypo-morphic signals in TP53 mutant samples. We defined this phenomenon as mutational mimicry (i.e. mutations in proteins mimicking those in established oncogenes) and we propose it as a tool for predicting tumor sensitivity/resistance to drugs.
    BRCA Biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • PIK3CA mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA H1047 • BRCA mutation • PIK3CA E542 • PIK3CA G1049R • PIK3CA Q546 • PIK3CA Q546K
    4years
    Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids. (PubMed, PLoS One)
    Thus, this ex vivo lung tumor spheroid model replicates the cellular and mutational tumor heterogeneity of human lung adenocarcinomas and can be used to assess the outgrowth of mutant subpopulations. Spheroid cultures with characterized mutant subpopulations could be used to investigate the efficacy of lung cancer combination therapies.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    BRAF V600E • KRAS mutation • PIK3CA mutation • BRAF V600 • KRAS G12D • PIK3CA H1047R • KRAS G12V • KRAS G12 • EGFR mutation + KRAS mutation • PIK3CA H1047
    |
    erlotinib
    4years
    PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4/6 inhibitors in metastatic breast cancer patients. (PubMed, Pharmacol Res)
    The findings of this pilot study suggest that the presence of a PI3K mutation in liquid biopsy correlates with a worse PFS in patients with ABC receiving CDK4/6i, and that liquid biopsy is a useful tool to suggests a better tailored pharmacological intervention.
    Clinical • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
    |
    PIK3CA mutation • PIK3CA H1047R • MSLN positive • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA C420R • PIK3CA E545A • PIK3CA Q546R • CDK4 mutation
    4years
    [VIRTUAL] Frequency and spectrum of doublePIK3CAsomatic mutations in metastatic breast cancer patients (SABCS 2020)
    Recently, alpelisib, a PI3Kα inhibitor, combined with hormonotherapy has improved progression-free survival in mutated advanced luminal BC... In our cohort, a wide spectrum of PIK3CA mutations was found in patients with metastatic breast cancer, suggesting the clinical relevance of molecular screening. Double PIK3CA mutations were identified in 15.8% of mutant tumors and maybe related to higher sensitivity to PI3K inhibitors. E545D mutation was always associated with a second mutation suggesting a different biological behavior.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • PIK3CA E542K • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542 • PIK3CA H1047L • PIK3CA C420R • PIK3CA E545A • PIK3CA E110K
    |
    Piqray (alpelisib)
    over4years
    Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov)
    P1/2, N=102, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2022 --> Dec 2022 | Trial primary completion date: Jan 2022 --> Dec 2022
    Clinical • Trial completion date • Trial primary completion date • Checkpoint inhibition • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib)
    over4years
    Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN (clinicaltrials.gov)
    P1/2, N=102, Not yet recruiting, National Cancer Institute (NCI)
    Clinical • New P1/2 trial • Checkpoint inhibition • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    PIK3CA mutation • PTEN mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Aliqopa (copanlisib)