Understanding the complex interplay between genetic alterations and immune markers is critical for optimizing therapeutic strategies and improving clinical outcomes. Further research is warranted to validate these findings and explore personalized treatment approaches in CRC.

11 months ago

Journal • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

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) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway)

PD-L1 expression • TP53 mutation • BRAF V600E • KRAS mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • BRAF V600 • PIK3CA H1047R • APC mutation • SMAD4 mutation • KRAS A146T

11ms

Durable disease regression with copanlisib treatment in PI3K-mutated metastasizing ameloblastoma: A case report. (PubMed, Rare Tumors)

Initial treatments, including carboplatin, etoposide, and taxane-based chemotherapy, were ineffective. After 76 cycles, she continues to tolerate therapy well with minimal adverse events. This case highlights the potential of targeted therapies such as copanlisib for treating METAM, providing a promising therapeutic option for patients with PIK3CA mutations.

11 months ago

Journal

BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PI3K (Phosphoinositide 3-kinases)

BRAF V600E • PIK3CA mutation • BRAF V600 • PIK3CA H1047R

carboplatin • etoposide IV • Aliqopa (copanlisib)

12ms

Direct comparison of an ultrasensitive real-time PCR assay with droplet digital PCR for the detection of PIK3CA hotspot mutations in primary tumors, plasma cell-free DNA and paired CTC-derived gDNAs. (PubMed, Front Oncol)

This assay can be performed in labs where digital PCR instrumentation is not available. In CTC-derived gDNA and paired plasma-cfDNA, PIK3CA mutations detected were not identical, revealing that CTC and plasma-cfDNA give complementary information.

12 months ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • EPCAM (Epithelial cell adhesion molecule)

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

12ms

PIK3CA mutation fortifies molecular determinants for immune signaling in vascular cancers. (PubMed, Cancer Gene Ther)

These molecular processes were disrupted by the PI3K-α specific inhibitor, alpelisib...Furthermore, we identified potential therapeutic vulnerabilities of PIK3CA mutations in response to PI3K-α inhibition mediated by MAPK signaling. In summary, we demonstrate that PIK3CA mutations perpetuate PI3K activation and reinforce immune enrichment to promote drug resistance in vascular cancers.

12 months ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8)

PIK3CA mutation • PIK3CA H1047R

Piqray (alpelisib)

12ms

Oncogenic PIK3CA corrupts growth factor signaling specificity. (PubMed, Mol Syst Biol)

PIK3CAH1047R did not only shift these responses to a higher mean but also enhanced signaling heterogeneity. We conclude that oncogenic PIK3CAH1047R corrupts information transfer in a growth factor-dependent manner and suggest new opportunities for tuning of receptor-specific PI3K pathway outputs for therapeutic benefit.

12 months ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IGF1 (Insulin-like growth factor 1) • IR (Insulin receptor)

PIK3CA H1047R

12ms

Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells. (PubMed, Breast Cancer Res)

These findings provide proof of principle that progenitors within the human breast luminal epithelial compartment may serve as a source of correctly positioned myoepithelial cells. This may prove useful in assessing the role of myoepithelial cells in breast tumor progression.

12 months ago

Journal

ALDH1A3 (Aldehyde Dehydrogenase 1 Family Member A3)

PIK3CA H1047R

12ms

PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma. (PubMed, J Clin Med)

The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

12 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • ATM mutation • PIK3CA H1047R • PTEN mutation • PIK3CA E545K • CDKN2A mutation • SMARCA4 mutation • PIK3CA E545 • PIK3CA E542

1year

PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

1 year ago

P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R

FoundationOne® CDx

carboplatin • paclitaxel • Bavencio (avelumab)

1year

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.

1 year 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)

1year

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%.

1 year 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

1year

Concordance Analysis of Non-Invasive determination techniques of PIK3CA and ESR1 mutations in patients with advanced luminal breast cancer. Study CANIPE (SABCS 2024)

However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039).

1 year ago

Clinical • Metastases • Discordant

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

HR positive • HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • ER mutation • ER D538G • PIK3CA E542K • ER Y537N • PIK3CA E545 • PIK3CA E542 • PIK3CA C420R • PIK3CA E545A • PIK3CA N345K • ER Y537C • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546K

AVENIO ctDNA Expanded Kit

Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib)

1year

Point mutations (PM), gene amplifications (GA) and variants of unknown significance (VUS) detected by next-generation sequencing (NGS) in a real-world sample of metastatic breast cancer (MBC) (SABCS 2024)

NGS of real-world patients reveals a broad spectrum of genomic abnormalities in MBC. TP53 and PIK3CA associate with TNBC and luminal MBC, respectively. Mutations in tumor suppressors are mostly distinct since there are many ways to induce loss-of-function.

1 year ago

Real-world evidence • Clinical • MSi-H Biomarker • Next-generation sequencing • Real-world • Metastases

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) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • FGF4 (Fibroblast growth factor 4) • AURKA (Aurora kinase A) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • GNAS (GNAS Complex Locus) • CCND2 (Cyclin D2) • RAD21 (RAD21 Cohesin Complex Component) • KDM5A (Lysine Demethylase 5A) • ZNF217 (Zinc Finger Protein 217) • FGF23 (Fibroblast Growth Factor 23) • GATA3 (GATA binding protein 3) • ZNF703 (Zinc Finger Protein 703)

TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • FGFR1 amplification • CCND1 amplification • FGF3 amplification

Guardant360® CDx