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BIOMARKER:

PIK3CA expression

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:
Related biomarkers:
5d
Vertical inhibition of p110α/AKT and N-cadherin enhances treatment efficacy in PIK3CA-aberrated ovarian cancer cells. (PubMed, Mol Oncol)
Importantly, co-targeting N-cadherin and p110α/AKT caused additive reduction in cell migration in vitro and metastases formation in vivo. Together, this study reveals the molecular pathways driven by the PIK3CA aberrations and the exploitable vulnerabilities in PIK3CA-aberrated serous ovarian cancer cells.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • YAP1 (Yes associated protein 1) • RAC1 (Rac Family Small GTPase 1) • CDH2 (Cadherin 2) • MAPK3 (Mitogen-Activated Protein Kinase 3)
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PIK3CA mutation • PIK3CA E545K • PIK3CA amplification • PIK3CA E545 • PIK3CA expression • AKT1 amplification • PIK3CA overexpression
29d
Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis. (PubMed, Sci Rep)
Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.
Journal
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CASP8 (Caspase 8) • APOBEC3B (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3B) • APOB (Apolipoprotein B)
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PIK3CA expression • HIF1A expression
1m
Association Between Recurrence of High-grade Squamous Intraepithelial Lesions of the Uterine Cervix and p16, C-myc and PIK3CA Proteins-A Single-center Retrospective Study. (PubMed, Cell Biochem Biophys)
Meanwhile, a prediction model F was constructed based on binary logistic regression analysis data with good fit, and through ROC curve analysis. It was found that p16, C-myc, PIK3CA, and logistic model F can effectively predict HPV16/18 (+), with model F having the best diagnostic performance.
Retrospective data • Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)
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MYC expression • PIK3CA expression
2ms
The potential of retinoic acid receptors as prognostic biomarkers and therapeutic targets in gastric cancer. (PubMed, Front Oncol)
In gastric cancer, high expression levels of RARα/RARβ/RARγ/RXRβ transcripts are associated with poor clinical and molecular characteristics as well as with reduced overall-survival. Our data are consistent with the idea that RARα, RARβ, RARγ and RXRβ represent potential prognostic markers and therapeutic targets of gastric cancer.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RARA (Retinoic Acid Receptor Alpha)
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TP53 expression • PIK3CA expression
7ms
Research of the unrecognised functions of miR-375 in prostate cancer cells. (PubMed, Cell Mol Biol (Noisy-le-grand))
In conclusion, miR-375 has anti-proliferative and cell migration inhibitory effects in prostate cancer. However, studies demonstrate that miR-375 may have tumor suppressor and oncogenic effects when considering cell molecular differences.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TSC1 (TSC complex subunit 1) • MIR375 (MicroRNA 375)
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PIK3CA expression
7ms
In Silico and In Vitro Study of Isoquercitrin against Kidney Cancer and Inflammation by Triggering Potential Gene Targets. (PubMed, Curr Issues Mol Biol)
Lastly, the RT-PCR and qRT-PCR findings showed a significant decrease in PTGS2, PIK3CA, and IGF1R gene expression, except for IL6 expression, following dose-dependent treatments with IQ. Thus, we can conclude that isoquercitrin inhibits the expression of PTGS2, PIK3CA, and IGF1R gene targets, which in turn controls kidney cancer and inflammation.
Preclinical • Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IL6 (Interleukin 6) • IGF1R (Insulin-like growth factor 1 receptor) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
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PIK3CA expression • PTGS2 expression • IL6 expression
7ms
Anticancer potential of grifolin in lung cancer treatment through PI3K/AKT pathway inhibition. (PubMed, Heliyon)
These anticancer effects were abolished by 740Y-P. Grifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)
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CCND1 expression • PIK3CA expression
7ms
Stromal rigidity stress accelerates pancreatic intraepithelial neoplasia progression and chromosomal instability via nuclear PTK2 localization. (PubMed, Am J Pathol)
Decreases of αSMA deposition in the CD248 knockout KPC mice remodel the tissue stroma and downregulated TOP2A expression in the epithelium. In summary, stromal stiffness induces the onset of cells-of-origin of cancer by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment against cells-of-origin cancer.
Journal • Stroma
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TOP2A (DNA topoisomerase 2-alpha) • PDX1 (Pancreatic And Duodenal Homeobox 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1) • PTK2 (Protein Tyrosine Kinase 2)
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KRAS G12D • TOP2A overexpression • KRAS G12 • MYC expression • PIK3CA expression
8ms
PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma. (PubMed, PPAR Res)
Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • PPARG (Peroxisome Proliferator Activated Receptor Gamma)
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PTEN expression • PIK3CA expression
8ms
PIK3CA mutation-driven immune signature as a prognostic marker for evaluating the tumor immune microenvironment and therapeutic response in breast cancer. (PubMed, J Cancer Res Clin Oncol)
The PDIS can be used as an effective prognostic model for predicting immunotherapy response to guide clinical decision-making.
Journal • BRCA Biomarker • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • BRCA mutation • PIK3CA expression
9ms
CD133 significance in glioblastoma development: in silico and in vitro study. (PubMed, Eur J Med Res)
CD133 can regulate the PI3K/Akt and MAPK pathways and modulate the clonogenicity, apoptosis, and cell cycle of GBM. Combining CD133 silencing with temozolomide treatment considerably increases apoptosis, arrests the cell cycle at the sub-G1, and suppresses migration of U87MG cells compared to temozolomide monotherapy.
Preclinical • Journal • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • mTOR (Mechanistic target of rapamycin kinase) • CDK4 (Cyclin-dependent kinase 4) • SOX2 • ANXA5 (Annexin A5) • MAPK3 (Mitogen-Activated Protein Kinase 3) • MMP16 (Matrix Metallopeptidase 16)
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PIK3CA expression • CD133 expression
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temozolomide
10ms
Prevalence, clinical characteristics, and treatment outcomes of patients with KRAS-mutated non-squamous NSCLC and PD-L1 expression: Real-life data analysis (ELCC 2024)
Analysis of progression-free survival (PFS) after the first line of treatment with immune checkpoint inhibitors (ICIs) in 30 pts with stage IV KRAS-mutated NSCLC and high PD-L1 showed a trend favoring patients presenting a co-mutation (mPFS 13.7mo KRAS co-mutated vs. 3.6mo in KRAS only; HR 0.26; CI 95% 0.09-0.070; p=0.19). Conclusions These findings emphasize the importance of further exploring PD-L1 role in KRAS mutated patients, especially by taking into account accompanying mutations in other genes evaluated by NGS.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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PD-L1 expression • TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • PTEN mutation • STK11 mutation • FGFR2 mutation • PD-L1 negative • KRAS wild-type • RAS wild-type • MET mutation • PIK3CA expression • KRAS expression
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VENTANA PD-L1 (SP263) Assay
10ms
Targeting MEK/COX-2 axis improve immunotherapy efficacy in dMMR colorectal cancer with PIK3CA overexpression. (PubMed, Cell Oncol (Dordr))
Our results identified that the PIK3CA hyperactivation in dMMR CRC upregulated COX-2 through MEK signaling, which inhibited CD8+ T cells infiltration and promoted tumor growth, together led to immunotherapy resistance. COX-2 or MEK inhibition may relieve therapy resistance and promote therapy efficacy of anti-PD-1/PD-L1 immunotherapy for treating dMMR CRC with PIK3CA overexpression or activating mutation.
Journal • PD(L)-1 Biomarker • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2)
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MSI-H/dMMR • PIK3CA mutation • CD8 expression • PIK3CA expression • PTGS2 expression • PIK3CA overexpression
10ms
PIK3CA regulates development of diabetes retinopathy through the PI3K/Akt/mTOR pathway. (PubMed, PLoS One)
The mutated SNP sites in patients with DR were mainly enriched in PI3K/AKT, calcium ion, and glutamatergic synaptic and cholinergic synaptic signaling pathways. The rs17849079 allele of PIK3CA is prone to C/T mutation where the C allele increases the risk of DR. High glucose activates the expression of PIK3CA and promotes the phosphorylation of PI3K, which leads to the phosphorylation of AKT and mTOR. These effects consequently increase VEGF expression and accelerate the development of DR. The C to T allele mutation in PIK3CA.rs17849079 can play a protective role and reduce the risk of DR.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TNFA (Tumor Necrosis Factor-Alpha) • PRKCE (Protein Kinase C Epsilon)
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PIK3CA mutation • PIK3CA expression • PIK3CA wild-type • VEGFA expression
12ms
Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer. (PubMed, Sci Rep)
Collectively, these results indicate an immune system function that may contribute to tumor survival. Our data induced a hypothesis that ARID1A and PIK3CA mutations' co-occurrence might predict responses to immunotherapy in luminal BC and, if validated, could guide immunotherapy development.
Journal • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • PRF1 (Perforin 1) • CD3E (CD3 Epsilon Subunit Of T-Cell Receptor Complex)
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PIK3CA mutation • ARID1A mutation • PIK3CA expression
12ms
Network pharmacology-based approach to investigate the molecular targets of essential oil obtained from lavender for treating breast cancer. (PubMed, Heliyon)
The AKT1 expression down-regulated while PIK3CA expression was increased in both cell lines. Our findings indicate that LEO has the ability to induce apoptosis by modulating the expression of PI3K-AKT signaling pathway in these cell lines.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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PIK3CA expression
12ms
Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer. (PubMed, Biomed Rep)
KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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BRAF mutation • NRAS mutation • PIK3CA mutation • KRAS wild-type • BRAF wild-type • RAS wild-type • NRAS wild-type • KRAS exon 2 mutation • PIK3CA expression • PIK3CA wild-type
12ms
Mutational and expressional association of the PIK3CA gene with the risk of breast cancer in the Pakistani population. (PubMed, Cell Mol Biol (Noisy-le-grand))
While multiallelic rs121913273 and rs121913279 showed a different trend for the studied population. For expressional analysis, PI3K showed over-expression in the cases while PIK3CA gene expression was observed to be significantly associated with pre-menopausal status.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PIK3CA mutation • PIK3CA expression
1year
Evaluation of tumor-infiltrating lymphocytes, PD-L1, and PIK3CA mutations and association with prognosis in HER2-positive early stage breast cancer. (PubMed, Acta Oncol)
Patients with low sTILs had a significantly worse overall survival (multivariate: HR 2.80; 95% CI 1.36-5.78; p = .02). Patients with low sTILs had a significantly poorer survival, despite adequate treatment with adjuvant therapy.
Journal • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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PD-L1 expression • HER-2 positive • PIK3CA mutation • PIK3CA expression • PD-L1 mutation
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VENTANA PD-L1 (SP263) Assay
1year
Matched multi-analyte and multi-omic liquid biopsy of cell-free DNA, circulating tumor cells and extracellular vesicles in HER2-positive metastatic breast cancer patients (SABCS 2023)
We successfully established a workflow for parallel isolation of multiple liquid biopsy analytes from a minimized blood volume in HER2+ mBC. Preliminary mRNA profile results for CTCs and EVs show the complementary nature of these two liquid biopsy analytes. Besides the multi-analyte nature of this workflow, the pending results for genomic and epigenomic information will show which one of the analytes, alone or in combination, will help to optimize therapy management in HER2+ mBC patients.
Clinical • Circulating tumor cells • Liquid biopsy • PARP Biomarker • Circulating tumor DNA • Tumor cell • Metastases • Biopsy • Cell-free DNA
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase) • ERCC1 (Excision repair cross-complementation group 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • AURKA (Aurora kinase A) • EPCAM (Epithelial cell adhesion molecule) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
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HER-2 positive • HR positive • HER-2 negative • PIK3CA expression • PIK3CA overexpression • PTEN mutation + HR positive
1year
Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial (SABCS 2023)
Patients with ER+/HER2- advanced or mBC who previously had 1-2 lines of endocrine therapy, and prior CDK4/6i, were randomized 1:1 to receive elacestrant or SOC (aromatase inhibitor or fulvestrant). Elacestrant showed significantly greater PFS when prior treatment duration with CDK4/6i was at least 12 months, suggesting prior exposure to CDK4/6i is a surrogate marker for endocrine sensitivity. In this population, elacestrant demonstrated superior efficacy, compared to SOC, even in patients with concomitant PIK3CA or TP53 mutations, expression of HER2 low, or presence of liver and/or lung metastases. These results suggest an active ER-driven pathway for this group despite the presence of other resistance mechanisms, where single-agent oral elacestrant could be an attractive option compared to combination therapies or intravenous HER2 low-targeted ADCs.
Clinical • P3 data • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
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TP53 mutation • HER-2 amplification • HER-2 negative • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • HER-2 underexpression • PIK3CA E545K • ER mutation • ESR1 mutation • PIK3CA E545 • PIK3CA E542 • PIK3CA expression
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fulvestrant • Orserdu (elacestrant)
1year
Molecular Analysis of Biliary Tract Cancers with the Custom 3' RACE-Based NGS Panel. (PubMed, Diagnostics (Basel))
Parallel analysis of 47 iCCA samples with the Illumina TruSight Tumor 170 kit confirmed good performance of our NGS panel. In conclusion, targeted RNA sequencing coupled with the 3' RACE technology is an efficient tool for the molecular diagnostics of BTCs.
Journal • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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PD-L1 expression • BRAF V600E • KRAS mutation • HER-2 amplification • PIK3CA mutation • BRAF V600 • HER-2 mutation • HER-2 expression • MET exon 14 mutation • FGFR2 mutation • FGFR1 expression • PIK3CA expression
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TruSight Tumor 170 Assay
1year
Defining the functional influence of endothelial cell-expressed oncogenic activating mutations on vascular morphogenesis and capillary assembly. (PubMed, Am J Pathol)
For example, activated Akt1 expression in ECs excessively stimulates lumen formation, decreases EC sprouting behavior, and show minimal pericyte recruitment with reduced mRNA expression of PDGF-BB, PDGF-DD, and endothelin-1; critical EC-derived factors known to stimulate pericyte invasion. We identify key signals controlling fundamental steps in capillary morphogenesis and maturation and, provide mechanistic details on why EC activating mutations induce a capillary deficiency state with abnormal lumens, impaired pericyte recruitment and basement deposition: predisposing stimuli for the development of vascular malformations.
Journal
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • JAK2 (Janus kinase 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • RHEB (Ras Homolog, MTORC1 Binding)
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KRAS mutation • PIK3CA mutation • PIK3CA expression • STAT3 expression • KRAS expression
1year
Targeting PI3Kα increases the efficacy of anti-PD-1 antibody in cervical cancer. (PubMed, Immunology)
Here, we report a case that continuous pembrolizumab monotherapy treatment induced complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer...PIK3CA mutations may predict the response of cervical cancer to PD-1 blockade. The efficacy of PI3Kα inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical and mechanistic investigations.
Journal • PD(L)-1 Biomarker • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD8 (cluster of differentiation 8) • IRF1 (Interferon Regulatory Factor 1)
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PD-L1 overexpression • PIK3CA mutation • PIK3CA E545K • PIK3CA E545 • IRF1 expression • PIK3CA expression • PD-L1 mutation
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Keytruda (pembrolizumab)
1year
Mutational Landscape of ER Receptor Negative Endometrial Cancer Patients Categorized as No Specific Molecular Profile (NSMP). (PubMed, Int J Radiat Oncol Biol Phys)
In this analysis, we show that GDC NSMP (ER low) tumors nearly all harbor a mutation in the PI3K-AKT-mTOR signaling pathway. Further we demonstrate that the most common gene mutation in the cohort, PIK3CA, is counterintuitively a marker of improved survival. Additionally, we show that within that this subpopulation, PIK3CA WT patients exhibit robustly upregulated gene expression programs dedicated to energy production, cell cycling, and division.
Journal
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ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • POLE (DNA Polymerase Epsilon)
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TP53 mutation • PIK3CA mutation • POLE mutation • MYC expression • MTOR mutation • PIK3CA expression
1year
CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA genes expression in colorectal cancer patients: novel diagnostic biomarkers. (PubMed, Eur Rev Med Pharmacol Sci)
Therefore, we can conclude that increased mRNA levels of CYP24A1, AHR, CPEB4, TRIP13, and PIK3CA in blood samples withdrawn from colorectal cancer patients could be a biomarker for the disease.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AHR (Aryl hydrocarbon receptor) • TRIP13 (Thyroid Hormone Receptor Interactor 13)
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PIK3CA expression • AHR expression
1year
Triple Reporter Assay: A Non-Overlapping Luciferase Assay for the Measurement of Complex Macromolecular Regulation in Cancer Cells Using a New Mushroom Luciferase-Luciferin Pair. (PubMed, Sensors (Basel))
However, only the multiplexed assessment revealed further complexities as stabilized p53 expression attenuates NF-κB transcriptional activity and thereby indirectly influences its regulation on the PIK3CA gene. Thus, this study suggests the importance of live cell multiplexed measurement of gene regulatory function using more than two luciferases to address more realistic situations in disease biology.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NFKB1 (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1)
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TP53 expression • PIK3CA expression
1year
Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer. (PubMed, Nat Commun)
Among hormone receptor-positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AR (Androgen receptor) • FGFR4 (Fibroblast growth factor receptor 4) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • PTK6 (Protein Tyrosine Kinase 6)
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HER-2 positive • HR positive • PIK3CA mutation • HR negative • FGFR4 mutation • PIK3CA expression
over1year
Mutational Landscape of ER Receptor Negative Endometrial Cancer Patients Categorized as No Specific Molecular Profile (NSMP) (ASTRO 2023)
In this analysis, we show that GDC NSMP (ER low) tumors nearly all harbor a mutation in the PI3K-AKT-mTOR signaling pathway. Further we demonstrate that the most common gene mutation in the cohort, PIK3CA, is counterintuitively a marker of improved survival. Additionally, we show that within that this subpopulation, PIK3CA WT patients exhibit robustly upregulated gene expression programs dedicated to energy production, cell cycling, and division.
Clinical
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ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • POLE (DNA Polymerase Epsilon) • MYCT1 (MYC Target 1)
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TP53 mutation • PIK3CA mutation • POLE mutation • MYC expression • MTOR mutation • PIK3CA expression
over1year
Loss of SATB2 and CDX2 expression is associated with DNA mismatch repair protein deficiency and BRAF mutation in colorectal cancer. (PubMed, Med Mol Morphol)
In conclusion, the lack of SATB2 and CDX2 expression in CRC was associated with MMR protein deficiency and BRAF mutation, but not with KRAS, NRAS and PIK3CA mutation. SATB2 and CDX2 are prognostic biomarkers in patients with CRC.
Journal • Mismatch repair
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDX2 (Caudal Type Homeobox 2) • SATB2 (SATB Homeobox 2)
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KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • BRAF wild-type • PIK3CA expression • CDX-2 expression
over1year
Urothelium-specific expression of mutationally activated Pik3ca initiates early lesions of non-invasive bladder cancer. (PubMed, Am J Pathol)
Furthermore, ssGSEA analysis of invasive human tumors showed those with mutant PIK3CA do not exhibit significantly increased PI3K/AKT pathway activity compared to wildtype PIK3CA tumors. Overall, these data suggest that Pik3ca can elicit early tumorigenic changes in the urothelium, but progression to invasion may require additional genetic alterations.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FOXA1 (Forkhead Box A1) • PPARG (Peroxisome Proliferator Activated Receptor Gamma)
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PIK3CA mutation • PIK3CA expression
over1year
Targeting PI3K Increases The Efficacy Of Anti-PD-1 Antibody In Cervical Cancer (ESGO 2023)
Here, we report a case that continuous pembrolizumab monotherapy treatment induced a complete remission of a recurrent cervical cancer patient with systemic metastasis and PIK3CA-E545K mutation, implying that PIK3CA mutation is potentially a biomarker for pembrolizumab treatment in cervical cancer...PI3Kα-specific inhibitors markedly activate immune microenvironment by regulating the PD-1/L1-related pathways and promotes CD8+ T cell differentiation, proliferation in Caski-CDXs with PIK3CA-E545K mutation. PI3Kα inhibitor significantly enhances the anti-tumor efficacy of PD-1 blockade in CDXs and PDXs.Conclusion The efficacy of PI3K inhibitors combined with PD-1 antibodies is promising in cervical cancer and warrants additional clinical investigations.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CD8 (cluster of differentiation 8) • IRF1 (Interferon Regulatory Factor 1)
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PD-L1 overexpression • PIK3CA mutation • PIK3CA E545K • PIK3CA E545 • IRF1 expression • PIK3CA expression • PD-L1 mutation
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Keytruda (pembrolizumab)
over1year
Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma. (PubMed, Front Oncol)
One patient each was treated with immune checkpoint inhibition (Mixed Response) and combination therapies of tipifarnib and ADT (SD) and alpelisib and ADT (PR). Combination therapies, PI3K-inhibitors and immune therapy warrant further investigation, ideally in clinical trials. Future research should consider this rare subgroup of SDC.
Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • AR (Androgen receptor) • HRAS (Harvey rat sarcoma viral oncogene homolog)
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PD-L1 expression • PIK3CA mutation • HRAS mutation • AR overexpression • AR expression • PIK3CA expression • HRAS overexpression • PIK3CA overexpression
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Piqray (alpelisib) • Zarnestra (tipifarnib)
over1year
The impact of PIK3CA mutations and PTEN expression on the effect of neoadjuvant therapy for postmenopausal luminal breast cancer patients. (PubMed, BMC Cancer)
PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)
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ER positive • HER-2 negative • PIK3CA mutation • PTEN mutation • PTEN expression • EGFR positive • PIK3CA expression • PIK3CA wild-type • PTEN-L • PGR expression • PTEN overexpression
over1year
Lipophagy-related gene RAB7A is involved in immune regulation and malignant progression in hepatocellular carcinoma. (PubMed, Comput Biol Med)
RAB7A may serve as a potential tumor prognostic and immune infiltration-related biomarker, predicting immunotherapy efficacy in certain cancer types, especially in HCC. Besides, RAB7A was a multi-pathway target involved in the malignant progression of HCC.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CCNA2 (Cyclin A2) • RAB7A (RAB7A, Member RAS Oncogene Family) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)
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PIK3CA expression • CDK6 expression
over1year
The adaptor protein VEPH1 interacts with the kinase domain of ERBB2 and impacts EGF signaling in ovarian cancer cells. (PubMed, Cell Signal)
Importantly, we found that loss of VEPH1 expression rendered ES2 cells less sensitive to BRAF and MEK inhibition. This study extends the range of adaptor function of VEPH1 to ERBB2, and indicates VEPH1 has differential effects on EGF signaling in ovarian cancer cells that may be influenced by driver gene mutations.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDH1 (Cadherin 1) • EGF (Epidermal growth factor) • CDH2 (Cadherin 2) • SNAI2 (Snail Family Transcriptional Repressor 2)
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KRAS mutation • HER-2 overexpression • BRAF mutation • HER-2 amplification • PIK3CA mutation • HER-2 expression • PIK3CA expression • PIK3CA overexpression
over1year
Anti-tumor effects of low-dose metronomic vinorelbine in combination with alpelisib in breast cancer cells. (PubMed, EXCLI J)
The p110α expression was downregulated or not affected in PIK3CA-mutated cell lines, and not significantly upregulated in PIK3CA wild-type cell lines. In conclusion, combination of low-dose metronomic VRL and alpelisib showed synergistic anti-tumor effects and significantly inhibited the growth of HR-positive, HER2-negative, PIK3CA-mutated BC cells, providing a rationale for further efforts to evaluate this combination in vivo.
Journal • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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EGFR mutation • HR positive • HER-2 negative • PIK3CA mutation • EGFR positive • PIK3CA expression • PIK3CA wild-type
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Piqray (alpelisib) • vinorelbine tartrate
over1year
KAT7 promotes radioresistance through upregulating PI3K/AKT signaling in breast cancer. (PubMed, J Radiat Res)
Moreover, overexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants promoted AKT phosphorylation at the Ser473 site, PIK3CA expression and radioresistance suppression due to KAT7 inhibition. In conclusion, KAT7 has huge prospects for clinical application as a new target for predicting radioresistance in breast cancer patients.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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PIK3CA mutation • AKT1 overexpression • PIK3CA expression • PIK3CA overexpression
over1year
Trimodal molecular analysis in single cells of a primary breast cancer cohort with ResolveOME ™ amplification (AACR 2023)
However, intriguingly, ResolveOME™ uncovered cells of stem-like identity harboring PIK3CA missense mutations as well as uncovered cells still formally identified as epithelial and harboring mutant PIK3CA but with differential expression profiles—indicative of cells morphing cell state. Finally, the TotalSeq™ antibody panel unveiled intercellular heterogeneity and interpatient heterogeneity both in cell-surface protein phenotype of immune cells and in epithelial identity and signaling.This ongoing study continues to catalog the three omic layers in increasing numbers of single cells and significantly expanding targeted surface-protein analysis harnessing the power of the single-cell united data to determine the “penetrance” of genomic changes in the context of cognate transcript and protein information, with the ultimate goals of defining DCIS to IDC transition factors as well as novel biomarker identification that may be exploited therapeutically.
BRCA Biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1)
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PIK3CA mutation • PIK3CA H1047R • PIK3CA expression • PIK3CA N345K
over1year
PIK3CA mutation induces immunogenicity and increases the immune checkpoint inhibitor response in urothelial carcinoma (AACR 2023)
UC with PIK3CA missense mutation exhibits a higher immunogenicity through enhancing MHC class I and B2M expression. PIK3CA missense mutation is a potential predictive marker for ICI response in UC.
Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • HLA-A (Major Histocompatibility Complex, Class I, A) • KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin) • MUC16 (Mucin 16, Cell Surface Associated) • HLA-B (Major Histocompatibility Complex, Class I, B) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • HLA-C (Major Histocompatibility Complex, Class I, C) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
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TMB-H • PIK3CA mutation • TMB-L • PIK3CA expression • PIK3CA wild-type
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ACTOnco