our Premium Content: News alerts, weekly reports and conference planners

GENE:

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

News alerts, weekly reports and conference planners

EPIK-B6: Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant in Japanese Men and Postmenopausal Women With Advanced Breast Cancer (clinicaltrials.gov)

P2, N=24, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jan 2025 --> Jul 2025

1 day ago

Trial primary completion date

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

Piqray (alpelisib) • fulvestrant

Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer (clinicaltrials.gov)

P2, N=69, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Aug 2025

1 day ago

Trial completion date

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

Piqray (alpelisib) • fulvestrant

FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer (clinicaltrials.gov)

P1, N=64, Recruiting, Regor Pharmaceuticals Inc. | N=18 --> 64

1 day ago

Enrollment change

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)

HER-2 negative • PIK3CA mutation

RGT-419B

Genomic Landscape of Fusions in Solid Tumors Detected by DNA and RNA Comprehensive Genomic Profiling at a Large Community Health System (AMP 2024)

The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.

2 days ago

Tumor mutational burden

ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion

TruSight Oncology 500 Assay

Detection of Common Hotspot Variants in PIK3CA and TP53 Using AGENA ClearSEEK on the MassARRAY System (AMP 2024)

Mutational hotspots are a recurrent feature in both genes which, due to positive selection during tumorigenesis, can be potentially exploited by targeted treatments, as has been demonstrated by the US Food and Drug Administration (FDA)-approved PI3K inhibitor alpelisib in advanced hormone-receptor positive (HR+) breast cancer... The AGENA ClearSEEK PIK3CA and TP53 Panels combine low hands-on time requirements with accurate data assessment, and provide a reliable tool for clinical trial evaluation of known actionable PIK3CA mutations and response to PI3K inhibitors in breast cancer, as well as for investigating the oncogenic activities of TP53 hotspot mutations and patient selection e.g., for cell cycle targeting therapies.

2 days ago

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

TP53 mutation • HR positive • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • TP53 R175H • PIK3CA E545 • PIK3CA E542 • TP53 R248Q • TP53 Y220C • TP53 R273H

ClearSEEK™ PIK3CA Panel

Piqray (alpelisib)

Diagnostic and Clinical Utility of OncoScan Microarray and NGS-Based Sequencing in Pediatric Solid Tumors: Children's Mercy Hospital Experience (AMP 2024)

OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.

2 days ago

Clinical • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • H3-3A (H3.3 Histone A)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • PIK3CA mutation • BRAF V600 • PTEN mutation • BRAF fusion

OncoScan™ CNV Assay

Clinical Validation of an Amplicon-Based Next-Generation Sequencing (NGS) Liquid Biopsy Assay for Predictive Testing in Patients with Solid Tumours (AMP 2024)

The assay shows good performance in detecting hotspot SNVs and small indels in ctDNA, and is suitable for clinical use. The limitation of bioinformatics pipelines in variant calling should be noted, and consideration can be given to run multiple pipelines in parallel to avoid missing out variants.

2 days ago

Clinical • Liquid biopsy • Next-generation sequencing • Biopsy

EGFR exon 20 insertion • EGFR exon 20 mutation

Oncomine™ Pan-Cancer Cell-Free Assay

The Agena iPlex HS Lung Panel on the MassARRAY System Is Able to Robustly Characterize the Molecular Profile of FFPE-Derived Lung Tumor Samples Previously Deemed QNS on Multiple NGS Platforms (AMP 2024)

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

2 days ago

Next-generation sequencing

KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • KRAS G12V • KRAS G12 • KRAS G13 • KRAS Q61 • KRAS deletion

TruSight Oncology 500 Assay

Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)

Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.

2 days ago

Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion

OncoExTra™ test

High Analytical Sensitivity and Specificity of the AVENIO Tumor Tissue CGP Automated Assay for Detecting Genomic Alterations in FFPE Tumor Tissue (AMP 2024)

The AVENIO CGP assay is an end-to-end platform for tumor genomic profiling, with proven high analytical sensitivity and specificity. Its superb performance makes it well suited for translational research, providing deep genomic analyses to accelerate cancer research.

2 days ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog)

HER-2 amplification • ALK fusion • NRAS G13

AVENIO Tumor Tissue CGP Kit • PGDx elio™ tissue complete assay

Low Limit of Detection Increases Detection and Reporting of Actionable Genomic Alterations (AMP 2024)

The ability to detect SNVs and indels below 5% VAF increases the diagnostic yield of actionable genomic alterations. This enables additional patients to consider FDA-approved on-label targeted therapies as a treatment option. Taken together, CGP assays that couple high sensitivity and low LOD can maximize identification of therapeutically relevant alterations across solid tumor types.

2 days ago

BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600 • PTEN mutation

OncoExTra™ test

Actionable Mutation Profiling in Solid Tumours in Australia Using Targeted Next-Generation Sequencing Panel (AMP 2024)

We demonstrated the feasibility of obtaining actionable information within a clinically meaningful turnaround time using a robust NGS solution. For samples with sufficient tumour content and DNA for testing (>90% of samples), Find It had an approximately 99% success rate. Actionable information provided by the panel could impact clinical management for 66% of advanced-stage cancer patients.

2 days ago

Next-generation sequencing

KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • RAS mutation • EGFR positive

Find It®

In silico exploration of phytochemicals as inhibitors for acute myeloid leukemia by targeting LIN28A gene: A cheminformatics study. (PubMed, Comput Biol Med)

This study elucidated that baicalein, 18β-glycyrrhizic, and limonin may be applied as potential candidates for targeting Lin28A as an active oncogene for acute myeloid leukemia.

8 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MAPK12 (Mitogen-Activated Protein Kinase 12)

The genomic landscape of papillary thyroid carcinoma on next-generation sequencing in patients undergoing total thyroidectomy. (PubMed, World J Surg)

This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

9 days ago

Journal • Next-generation sequencing

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • CDH1 (Cadherin 1)

BRAF mutation • PIK3CA mutation • ALK mutation • PTCH1 mutation

10d

Design, synthesis, and biological evaluation of 2,4-dimorpholinopyrimidine-5-carbonitrile derivatives as orally bioavailable PI3K inhibitors. (PubMed, Front Pharmacol)

Compound 17p demonstrated comparable PI3Kα inhibitory activity (IC50: 31.8 ± 4.1 nM) to the positive control, BKM-120 (IC50: 44.6 ± 3.6 nM)...In a pharmacokinetic study, 17p was stable (T ½: 2.03 h) and showed high bioavailability (46.2%). Collectively, these results indicate that 17p could be a promising PI3K agent for cancer treatment.

10 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)

buparlisib (AN2025)

10d

The potential role of next-generation sequencing in identifying MET amplification and disclosing resistance mechanisms in NSCLC patients with osimertinib resistance. (PubMed, Front Oncol)

The known resistance mechanisms, including MET amplification, EGFR (C797S, L718Q/R), TP53, CDK4, CDK6, CDKN2A, BRAF, KRAS, NRAS and PIK3CA mutations were also disclosed in our cohort. NGS assay can achieve a high concordance with FISH in MET amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.

10 days ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)

TP53 mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR C797S • EGFR L718Q • BRAF amplification • EGFR C797S + MET amplification

Tagrisso (osimertinib)

10d

Comprehensive liquid biopsy analysis for monitoring NSCLC patients under second-line osimertinib treatment. (PubMed, Front Oncol)

AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.

10 days ago

Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker • Biopsy

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • B2M (Beta-2-microglobulin) • FOXA1 (Forkhead Box A1) • PIM1 (Pim-1 Proto-Oncogene) • VIM (Vimentin) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT19 (Keratin 19) • RASSF1 (Ras Association Domain Family Member 1) • WIF1 (WNT Inhibitory Factor 1) • BRMS1 (BRMS1 Transcriptional Repressor And Anoikis Regulator)

PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • EGFR T790M • MET mutation • KRAS G12 • EGFR mutation + PIK3CA mutation • HER-2 amplification + PD-L1 expression • VIM expression • HER-2 amplification + MET amplification • RASSF1 methylation

Tagrisso (osimertinib)

10d

Breast cancer genomic analyses reveal genes, mutations, and signaling networks. (PubMed, Funct Integr Genomics)

We found that BC panels share only seven genes. These findings show that BC arises from genetic disruptions evident in BC signaling and protein networks.

10 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • MUC16 (Mucin 16, Cell Surface Associated) • AHNAK2 (AHNAK Nucleoprotein 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • USH2A (Usherin) • GATA3 (GATA binding protein 3) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1)

TP53 mutation

10d

Marjolin's Ulcer: Comprehensive Genomic Profiling Reveals Potentially Actionable Biomarkers and Mutational Similarity to HPV(–) Vulvar Squamous Cell Carcinoma (ASDP 2024)

Overall, muSCC shows similar genomic alterations and TMB to HPV(–) vSCCs. CGP of inflammation-associated SCCs may be important to more fully inform therapeutic options and stratification in clinical trials.

10 days ago

Tumor mutational burden

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • FAT1 (FAT atypical cadherin 1) • CASP8 (Caspase 8)

TP53 mutation

FoundationOne® CDx

11d

Recombinase polymerase amplification in combination with electrochemical readout for sensitive and specific detection of PIK3CA point mutations. (PubMed, Anal Chim Acta)

Characterization of the two different approaches in terms of sensitivity results in comparable detection limits (229 copies μL-1 and 224 copies μL-1, respectively), though RPA followed by lambda exonuclease digestion yields significantly higher currents. Finally, this method, together with a designed wild-type blocking oligo that inhibits binding of the wild-type target DNA during probe-target hybridization, allows for detecting the PIK3CA point mutations H1047R, E545K, and E542K in the presence of wild-type target DNA when the proportion of mutant target DNA is >20%.

11 days ago

Journal • Combination therapy

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • PIK3CA E542K • PIK3CA E545 • PIK3CA E542

11d

Genomes and epigenomes of matched normal and tumor breast tissue reveal diverse evolutionary trajectories and tumor-host interactions. (PubMed, Am J Hum Genet)

These groups exhibited distinct genomic and epigenomic characteristics in both NAT and tumor samples. Specifically, NAT samples in the shared-tree group showed higher number of mutations, while NAT samples belonging to the multiple-tree group showed a less inflammatory tumor microenvironment (TME), characterized by a higher proportion of regulatory T cells (Tregs) and lower presence of CD14 cell populations. In summary, our findings highlight the diverse evolutionary history in BC NAT/tumor pairs and the impact of field cancerization and TME in shaping the genomic evolutionary history of tumors.

11 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CD14 (CD14 Molecule) • GATA3 (GATA binding protein 3)

TP53 mutation • PIK3CA mutation

11d

TIFA: Preventing High Blood Sugar in People Being Treated for Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=15, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

11 days ago

Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HR positive • HER-2 negative • PIK3CA mutation • PTEN mutation + HR positive • HER-2 negative + HR positive + PIK3CA mutation

Piqray (alpelisib) • fulvestrant

11d

Immune cell infiltration and drug sensitivity in PIK3CA-mutated esophageal squamous cell carcinoma: A TCGA database analysis. (PubMed, Hum Immunol)

Additionally, ESCC cells harboring PIK3CA mutations exhibited reduced sensitivity to p38/JNK MAPK inhibitors compared to those with wild-type PIK3CA. Collectively, our in silico analysis suggests that mutational PIK3CA plays a role in resistance to p38 and JNK MAPK inhibitors in ESCC.

11 days ago

Journal • Tumor mutational burden • Immune cell

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CD4 (CD4 Molecule)

PIK3CA mutation

12d

Spatial organization of PI3K-PI(3,4,5)P3-AKT signaling by focal adhesions. (PubMed, Mol Cell)

Furthermore, combined inhibition of p110α and FAK results in a more potent inhibitory effect on cancer cells. Thus, our results unveil a growth-factor independent, compartmentalized organization mechanism for PI3K-PI(3,4,5)P3-AKT signaling.

12 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

14d

ATP-competitive inhibitors of PI3K enzymes demonstrate an isoform selective dual action by controlling membrane binding. (PubMed, Biochem J)

Using FRET and Biolayer Interferometry assays, we show that a class of ATP-site directed inhibitors represented by GSK2126458 block the growth factor activated PI3KαWT membrane interaction, an activity dependent on the ligand forming specific ATP-site interactions...We find that an ATP substrate analogue can increase the wild type PI3Kα membrane interaction, uncovering a substrate based regulatory event that can be mimicked by different inhibitor chemotypes. Our findings, together with the discovery of small molecule allosteric activators of PI3Kα illustrate that PI3Kα membrane interactions can be modulated by factors related to ligand binding both within the ATP site and at allosteric sites.

14 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation

omipalisib (GSK2126458)

14d

Non-small cell lung carcinoma with co-expression of TTF1 and p40: a clinicopathological analysis of six cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

14 days ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • EML4 (EMAP Like 4) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1)

EGFR mutation • NRAS mutation • PIK3CA mutation • ALK mutation • NKX2-1 expression • TTF1 expression

15d

Molecular and Clinicopathologic Characterization of HER2-overexpressed Squamous Cell Carcinoma of the Cervix. (PubMed, Int J Gynecol Pathol)

Next-generation sequencing of the 3 HER2-amplified tumors showed amplification of various genes, including CD274, JAK2, BIRC3, and ERBB2, and a PIK3CA missense mutation. In summary, HER2 immunohistochemistry is a reliable predictive marker of HER2 amplification in cervical cancer.

15 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • JAK2 (Janus kinase 2) • BIRC3 (Baculoviral IAP repeat containing 3)

HER-2 overexpression • HER-2 amplification • PIK3CA mutation

16d

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. (PubMed, N Engl J Med)

In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).

16 days ago

Clinical • Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HR positive • HER-2 negative • PIK3CA mutation • PIK3CA mutation + HR positive • EGFR positive • HR positive + HER-2 negative • PTEN mutation + HR positive • HER-2 negative + HR positive + PIK3CA mutation

Ibrance (palbociclib) • fulvestrant • Itovebi (inavolisib)

16d

Banxia xiexin decoction prevents the development of gastric cancer. (PubMed, World J Clin Oncol)

BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

16 days ago

Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • IL6 (Interleukin 6)

EGFR expression • BCL2 expression • IL6 expression

capecitabine • LY294002

16d

Sialadenopapillary Ductal Tumors: Unifying the Spectrum of Sialadenoma Papilliferum-like Tumors With Low Malignant Potential. (PubMed, Am J Surg Pathol)

These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.

16 days ago

Journal

BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • NCOA4 (Nuclear Receptor Coactivator 4)

BRAF V600E • PIK3CA mutation • BRAF V600 • RET fusion • NCOA4-RET fusion

16d

BTCRC-BRE19-409: Alpelisib (BYL719) in Combination With Continued Endocrine Therapy Following Progression on Endocrine Therapy in Hormone Receptor Positive, HER2 Negative, PIK3CA Mutant Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=44, Recruiting, Marina N Sharifi | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

16 days ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

HER-2 amplification • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative • PTEN mutation + HR positive • HER-2 negative + HR positive + PIK3CA mutation

Piqray (alpelisib) • fulvestrant

18d

Clinicopathogenomic analysis of PI3K/AKT/PTEN-altered luminal metastatic breast cancer in Japan. (PubMed, Breast Cancer)

These results are crucial for characterizing candidates for AKT pathway-targeted molecular therapies and conceptualizing optimal treatment strategies. Clinical trial registration: This study is an observational study and is therefore not registered with the clinical trials registration.

18 days ago

Journal • Tumor mutational burden • BRCA Biomarker • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog)

BRCA2 mutation • BRCA1 mutation • PTEN mutation • BRCA1 expression • BRCA2 expression

18d

Whole-exome profiles of inflammatory breast cancer and pathological response to neoadjuvant chemotherapy. (PubMed, J Transl Med)

This is the first study aiming at identifying correlations between the WES data of IBC samples and the achievement of pCR to NACT. Our results, obtained in this 44-sample series, suggest a few subtle genomic alterations associated with pathological response. Additional investigations are required in larger series.

18 days ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • NLRP3 (NLR Family Pyrin Domain Containing 3)

TP53 mutation • PIK3CA mutation

18d

Association of mutation profiles with metastasis in patients with non-small cell lung cancer. (PubMed, Front Oncol)

Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.

18 days ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • ALK mutation • MET mutation • EGFR mutation + PIK3CA mutation

19d

Detection of PIK3CA hotspot mutations in canine mammary tumors using droplet digital PCR: tissue validation and liquid biopsy feasibility. (PubMed, Sci Rep)

These results highlight the viability of liquid biopsy as a minimally invasive method for monitoring PIK3CA mutations in canine patients. The study suggests that liquid biopsy techniques hold significant promise for improving the early detection and monitoring of canine cancers, warranting further research to refine these methods and explore their applications in canine cancer diagnostics and treatment.

19 days ago

Journal • Liquid biopsy • Biopsy

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

PIK3CA mutation • PIK3CA H1047R

19d

The Clinical and Molecular Landscape of Rosette-Forming Glioneuronal Tumors. (PubMed, Biomedicines)

This study concludes that while current treatment strategies focus on surgical resection, integrating molecular diagnostics and targeted therapies may be essential for managing recurrent or refractory RGNTs. Future research should explore the impact of various gene mutations on tumor behavior and their correlation with clinical outcomes, to optimize individualized therapeutic strategies and improve patient survival and quality of life.

19 days ago

Review • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • TERT (Telomerase Reverse Transcriptase) • SYP (Synaptophysin) • GFAP (Glial Fibrillary Acidic Protein)

PIK3CA mutation • FGFR1 mutation • TERT mutation

19d

A Novel AKT1, ERBB2, ESR1, KRAS, PIK3CA, and TP53 NGS Assay: A Non-Invasive Tool to Monitor Resistance Mechanisms to Hormonal Therapy and CDK4/6 Inhibitors. (PubMed, Biomedicines)

Based on our findings, the liquid biopsy analysis using the PQS panel seems to be both feasible and accurate, demonstrating a strong sensitivity in detecting mutations. This exploratory analysis of the clinical outcome associated to the mutational status of patients highlights the potential of molecular analysis on liquid biopsy for disease monitoring, although further validation with a larger patient cohort is necessary to confirm these preliminary observations.

19 days ago

Journal • Next-generation sequencing

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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

HR positive • HER-2 negative • PIK3CA mutation

19d

Molecular Mechanism of Radioresponsiveness in Colorectal Cancer: A Systematic Review. (PubMed, Genes (Basel))

Gene set analysis shows that nearly half of the genes were involved in apoptosis, DNA damage response and repair, inflammation and cancer metabolism molecular pathways that could affect cancer radioresponse. The gene cohort identified in this study may be used as a foundation for future works focusing on the molecular mechanism of specific pathways contributing to the radioresponse of CRC.

19 days ago

Review • Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FLT3 (Fms-related tyrosine kinase 3) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA) • PTGS1 (Prostaglandin-Endoperoxide Synthase 1)

19d

Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal Carcinoma: The Way Forward for Personalized Treatment? A Single-Center Experience. (PubMed, Int J Mol Sci)

In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.

19 days ago

Journal • Next-generation sequencing • 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) • FGFR2 (Fibroblast growth factor receptor 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • JAK1 (Janus Kinase 1)

KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • FGFR2 mutation • KRAS G12 • ERBB3 mutation • MTOR mutation

19d

Clinical and Histopathological Features of Thyroid Cancer with TERT Promoter Molecular Alterations in Isolation Versus with Concurrent Molecular Alterations: A Multicenter Retrospective Study. (PubMed, Cancers (Basel))

Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

19 days ago

Retrospective data • Journal

BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TERT (Telomerase Reverse Transcriptase) • RAS (Rat Sarcoma Virus) • GNAS (GNAS Complex Locus) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked) • TG (Thyroglobulin)

BRAF V600E • BRAF V600 • TERT mutation

21d

Personalized Treatment Strategies via Integration of Gene Expression Biomarkers in Molecular Profiling of Laryngeal Cancer. (PubMed, J Pers Med)

This review seeks to provide a comprehensive framework for promoting personalized cancer therapy by combining the most recent data on gene expression profiling in laryngeal cancer. Molecularly guided treatment options may enhance patient outcomes.

21 days ago

Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • CD44 (CD44 Molecule) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)

PIK3CA mutation • NOTCH1 mutation • CD44 expression

21d

Higher risk of recurrence in early-stage breast cancer patients with increased levels of ribosomal protein S6. (PubMed, Sci Rep)

When assessed in combination with lymph node status, the predictive capacity was higher compared to both univariate models individually. In conclusion, pS6 could represent a novel independent marker for predicting recurrence risk in luminal breast cancer.

21 days ago

Observational data • Retrospective data • Journal

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RPS6 (Ribosomal Protein S6)

HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • AKT1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive • HER-2 negative + HR positive + AKT1 mutation