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    BIOMARKER:

    AKT1 mutation

    i
    Other names: AKT1, AKT, PKB, PRKBA, RAC, V-akt murine thymoma viral oncogene homolog 1
    Entrez ID:
    207
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    8d
    CRAFT: the NCT-PMO-1602 Phase II Trial (clinicaltrials.gov)
    P2, N=175, Active, not recruiting, German Cancer Research Center | Recruiting --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
    |
    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) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • PI3K (Phosphoinositide 3-kinases)
    |
    BRAF V600E • TMB-H • PD-L1 overexpression • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • BRAF V600 • RET fusion • ALK rearrangement • BRAF V600K • AKT1 mutation • PD-L1 amplification • ALK rearrangement + PIK3CA mutation
    |
    Herceptin (trastuzumab) • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Alecensa (alectinib) • Perjeta (pertuzumab) • Cotellic (cobimetinib) • ipatasertib (RG7440) • Itovebi (inavolisib)
    27d
    A case of familial adenomatous polyposis in an adult male with Lynch-like syndrome (PubMed, Zhonghua Wei Chang Wai Ke Za Zhi)
    The patient underwent laparoscopic total colectomy with abdominoperineal resection and end ileostomy, then received 4 cycles adjuvant chemotherapy of oxaliplatin with capecitabine. This patient was followed up to April 2024 and performed well without abnormalities in serum cancer biomarkers and radiological examinations.
    Journal • Tumor mutational burden
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MLH1 (MutL homolog 1) • PTCH1 (Patched 1)
    |
    KRAS mutation • TMB-H • PIK3CA mutation • PTCH1 mutation • AKT1 mutation
    |
    capecitabine • oxaliplatin
    2ms
    Development of a method for detecting genetic mutations in early breast cancer using Plasma-Safe-SeqS technology and its clinical application. (SABCS 2024)
    In addition to the postoperative blood sampling described above, we are currently conducting (1) postoperative blood sampling and (2) postoperative blood sampling after completion of adjuvant therapy. We aim to ascertain whether this mutation can serve as a predictive marker for response to postoperative chemotherapy or recurrence, especially in hormone-positive breast cancer patients at high risk of recurrence.
    Clinical
    |
    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)
    |
    TP53 mutation • HER-2 negative • PIK3CA mutation • AKT1 mutation
    |
    OncoGuide™ NCC Oncopanel System
    2ms
    Clinicogenomic landscape and function of PIK3CA, AKT1, and PTEN mutations in breast cancer (SABCS 2024)
    Background The AKT inhibitor capivasertib was recently approved in the 2L+ setting for patients (pts) with hormone receptor-positive metastatic breast cancer with alterations in PIK3CA, AKT1, and/or PTEN...However, one-third of patients have variants beyond E542, E545, and H1047 with less certainty about targetability. The preponderance of rare PIK3CA mutations and co-occurrences between PIK3CA, AKT1, and PTEN with genes outside the PI3K pathway merits functional investigation.
    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) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • SOX2 • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
    |
    TP53 mutation • HR positive • HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PTEN mutation • PIK3CA E545K • PIK3CA E542K • AKT1 mutation • PIK3CA E545 • PIK3CA H1047 • PIK3CA E542
    |
    FoundationOne® CDx
    |
    Truqap (capivasertib)
    2ms
    Tumor genomics in young patients with metastatic breast cancer (SABCS 2024)
    In EMBRACE, differences in mutational frequency of several genes were observed by age at MBC diagnosis among patients with recurrent MBC, most notably for HR+/HER2- patients. Lower OS among younger recurrent MBC patients may be driven by these differences, particularly by high frequency of TP53 mutations in this age group. Further investigation of these genes is warranted to elucidate pathways leading to metastasis and to improve survival for young MBC patients.
    Clinical • Tumor mutational burden • BRCA Biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • 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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • BRCA1 mutation • TMB-H • HER-2 negative • PIK3CA mutation • HER-2 mutation • AKT1 mutation • CDH1 mutation
    |
    OncoPanel™ Assay
    2ms
    A case of sequential alpelisib and capivasertib in a patient with metastatic breast cancer harboring both a PIK3CA and AKT mutations (SABCS 2024)
    Therapies targeting mutations in this pathway approved in conjunction with endocrine therapy include alpelisib, everolimus and capivasertib...She received nab-paclitaxel/atezolizumab for 4 months, letrozole and abemaciclib for 2 months, letrozole alone for 6 months, and letrozole and ribociclib for 6 weeks. Given presence of PIK3CA mutation, 4th line treatment with fulvestrant and alpelisib was planned...After progressing on capecitabine after 2 months, alpelisib with exemestane was initiated...Due to a low ejection fraction despite work with cardiooncology, she was not a candidate for trastuzumab deruxtecan. She progressed on oral cyclophosphamide and methotrexate after 2 months and Sacituzumab govitecan after 3 months...Comprehensive biomarker assessment is needed to identify patients who may benefit from sequential therapies. There is a need for trials comparing therapies that target the PI3K pathway at distinct points, potential sequencing of these therapies, and the optimal sequence strategy.
    Clinical • PD(L)-1 Biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor)
    |
    ER positive • HR positive • PIK3CA mutation • PIK3CA E545K • AKT1 E17K • AKT1 mutation • PIK3CA E545 • PGR negative
    |
    Guardant360® CDx • MSK-IMPACT
    |
    Tecentriq (atezolizumab) • everolimus • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Piqray (alpelisib) • Verzenio (abemaciclib) • albumin-bound paclitaxel • cyclophosphamide • Kisqali (ribociclib) • fulvestrant • Truqap (capivasertib) • methotrexate • letrozole • Trodelvy (sacituzumab govitecan-hziy) • exemestane
    2ms
    Real-World Molecular Profiling After CDK4/6 Inhibition in Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE Study (SABCS 2024)
    Over two-thirds of pts progressing on CDK4/6i present with ESCAT I-II level alterations detected via tumor or liquid biopsy. Notably, 15-25% of these pts exhibit cooccurring targetable alterations. In our study, the most frequently targeted alteration was PIK3CA mut, due to lack of approval for targeted therapies for other ESCAT I-II alterations in Spain during the study period.
    Clinical • Real-world evidence • BRCA Biomarker • Real-world • Metastases
    |
    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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 negative • PIK3CA mutation • PTEN mutation • AKT1 mutation
    |
    FoundationOne® CDx • Guardant360® CDx
    2ms
    Genomic predictors of response among patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC) receiving the AKT inhibitor (AKTi) ipatasertib combined w/ endocrine therapy & a CDK4/6 inhibitor (CDK4/6i) in TAKTIC trial (SABCS 2024)
    TAKTIC was a phase Ib open-label trial evaluating ipatasertib in combination with fulvestrant, an aromatase inhibitor, or fulvestrant + palbociclib, in participants with HR+/HER2- MBC who received ≥1 line of prior therapy for MBC and had exposure to CDK4/6i (NCT03959891). Genomic insights using NGS suggest that MBC post-CDK4/6i is more susceptible to an AKTi-based treatment with ipatasertib in the presence of a PI3K/AKT/PTEN pathway mutation, whereas alterations in FGFR1 are associated with worse outcomes. This effort is one of very few studies prospectively evaluating mediators of AKTi response, an area of active interest given changes in the therapeutic landscape. The results presented here are hypothesis-generating; future work is underway to further expand upon these data.
    Clinical • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDK4 (Cyclin-dependent kinase 4)
    |
    HR positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • AKT1 mutation
    |
    Guardant360® CDx
    |
    Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)
    2ms
    Prevalence of PIK3CA/AKT1/PTEN and other genomic alterations in primary and recurrent tumor tissue: exploratory analysis from the Phase 3 CAPItello-291 clinical trial (SABCS 2024)
    Background Based on the positive results from the CAPItello-291 trial, capivasertib plus fulvestrant is a treatment option for adult patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on an endocrine-based regimen and whose tumors harbor one or more alterations in PIK3CA, AKT1, or PTEN. Consistent with the literature, recurrent tissues were enriched for ESR1, BRCA2, GATA3, CDKN2A, and SMAD4 alterations, indicating a potential role for these gene alterations in driving disease recurrence. The PIK3CA/AKT1/PTEN-altered cohort was enriched for CDH1 mutations while the non-altered cohort was enriched for alterations in cell cycle-related genes previously associated with endocrine and cyclin-dependent kinase 4/6 inhibitor resistance.
    Clinical • P3 data • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    PIK3CA mutation • PTEN mutation • ER mutation • AKT1 mutation • CDH1 mutation
    |
    FoundationOne® CDx
    |
    fulvestrant • Truqap (capivasertib)
    2ms
    Prevalence of actionable genomic alterations (GA) and predictive value of tumor mutational burden (TMB) for immune checkpoint inhibitor (ICI) effectiveness in HR(+)HER2(-) metastatic breast cancer (MBC) (SABCS 2024)
    Background: Pembrolizumab, an anti-PD1 antibody ICI is an FDA-approved option for patients with HR(+)HER2(-) MBC who have exhausted standard of care options and have high TMB (≥10 mut/mb, FoundationOne®CDx)... About 70% of TBx harbor at least one GA with established clinical utility. Pts with TMB10+ vs. TMB<10 had more favorable PFS and rwOS on ICI.
    Checkpoint inhibition • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • 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) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • AKT1 mutation • HRD signature • BRCA1 fusion
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    2ms
    Predicting response to capivasertib in AKT1 mutant advanced breast cancer (SABCS 2024)
    Allelic imbalance at the AKT1 locus and clonal dominance of the AKT1 mutation were associated with progression free survival (PFS) in plasmaMATCH Cohorts C (capivasertib plus fulvestrant) and D (capivasertib alone) combined. Breast cancers with mutations in AKT1 frequently have allelic imbalance favouring the mutation, resulting in increased expression of mutant transcript. Allelic imbalance of AKT1, and/or clonally dominant AKT1 mutations, were prognostic for significantly greater PFS of patients treated with capivasertib.
    Metastases
    |
    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) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    TP53 mutation • PIK3CA mutation • AKT1 mutation • AKT1 Q79K
    |
    Guardant360® CDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    fulvestrant • Truqap (capivasertib)
    2ms
    Multiple Pulmonary Sclerosing Pneumocytomas (PSPs): A Comprehensive Analysis of Clinicopathological Characteristics and Whole-exome Sequencing (WES) Results. (PubMed, Am J Surg Pathol)
    In conclusion, this retrospective study is the largest series of multiple PSP cases and provides new insights into the genomic underpinning of PSP. This work has a potential to broaden our understanding of the pathogenesis and development of these lesions and warrants analysis in larger cohorts.
    Journal
    |
    ARID1A (AT-rich interaction domain 1A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    ARID1A mutation • AKT1 mutation
    2ms
    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.
    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
    2ms
    The landscape of genomic alterations and their phenotype associations in high-risk localized prostate cancer in the Genomic Umbrella Neoadjuvant Study (PCF 2024)
    Transcriptomes distinguished ETS -fused tumors from SPOP mutants, and PTEN loss from PTEN/AKT1 mutations. Inferred relationships between specific genomic alterations and gene expression signatures of luminal/basal subtypes and of biological pathways/processes, including AR signaling, proliferation, and plasticity signatures, provide a basis to understand differences in treatment response and inform biomarker-guided treatment strategies.
    Clinical • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDK12 (Cyclin dependent kinase 12) • ERG (ETS Transcription Factor ERG) • SPOP (Speckle Type BTB/POZ Protein) • FOXA1 (Forkhead Box A1) • TMPRSS2 (Transmembrane serine protease 2)
    |
    CDK12 mutation • AKT1 mutation • AR expression • SPOP mutation • TMPRSS2-ERG fusion • FOXA1 mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    3ms
    Novel Mutations in AKT1 Gene in Prostate Cancer Patients in Jordan. (PubMed, Curr Issues Mol Biol)
    It is concluded that there is a high frequency of AKT1 mutation in PC patients in Jordan with two novel missense mutations in the Pleckstrin homology (PH) domain. E17K hotspot mutation was not detected in any tested samples, which underlined the significant role of mutations in other AKT1 exons in PC development.
    Journal
    |
    AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    AKT1 mutation
    3ms
    A071401: Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients with Progressive Meningiomas (clinicaltrials.gov)
    P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PTCH1 (Patched 1) • CDK4 (Cyclin-dependent kinase 4) • NF2 (Neurofibromin 2) • SMO (Smoothened Frizzled Class Receptor) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
    |
    PIK3CA mutation • PTEN mutation • CDKN2A mutation • PTCH1 mutation • NF2 mutation • AKT1 mutation • SMO mutation • PIK3CA mutation + PTEN mutation • CDK4 mutation
    |
    Verzenio (abemaciclib) • Truqap (capivasertib) • Erivedge (vismodegib) • GSK2256098
    5ms
    Characterizing the genomic landscape of breast cancer in an Irish cohort of patients (ESMO 2024)
    We present the largest study of BC variant frequencies in a cohort of Irish breast cancer patients to date and confirm NGS is feasible and identifies clinically relevant and actionable variants. We confirm that the frequency of PIK3CA alterations, in addition to codon specificity, are comparable to those observed in European and US cohorts and demonstrate that the detection of clinically relevant biomarkers is not confined to ER positive HER2 negative BC. The tissue failure rate (19%) underscores the need for cfDNA testing to identify the expanding range of actionable targets in BC to improve access to emerging targeted therapies and biomarker-driven clinical trials.
    Clinical • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    HER-2 positive • ER positive • HER-2 amplification • HER-2 negative • PIK3CA mutation • HER-2 S310F • ESR1 mutation • AKT1 mutation • HER-2 D769Y • HER-2 L869R • ER positive + HER-2 negative • HER-2 negative + ER positive • HER-2 negative + ER positive + ESR1 mutation
    |
    Oncomine Focus Assay
    8ms
    Correlation of Molecular Status with Preoperative Olfactory Function in Olfactory Groove Meningioma. (PubMed, Cancers (Basel))
    The study highlights PSH and perifocal oedema's significant effect on olfactory function in OGM patients but finds no link between olfactory impairment and tumour mutations, possibly due to the small sample size. This suggests that age and gender affect olfactory impairment. Additional research with a larger group of participants is needed to explore the impact of OGM driver mutations on olfactory performance.
    Journal
    |
    AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMO (Smoothened Frizzled Class Receptor)
    |
    AKT1 mutation • SMO mutation
    8ms
    Meningioma: current updates on genetics, classification, and mouse modeling. (PubMed, Ups J Med Sci)
    Most meningioma mouse models are based on patient-derived xenografts and only recently have new genetically engineered mouse models of meningioma been developed that will aid in the systematic evaluation of specific mutations found in meningioma and their impact on tumor behavior. In this article, we review recent advances in the understanding of meningioma biology and classification and highlight the most common genetic mutations, as well as discuss new genetically engineered mouse models of meningioma.
    Preclinical • Review • Journal
    |
    AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NF2 (Neurofibromin 2) • KLF4 (Kruppel-like factor 4)
    |
    AKT1 mutation
    9ms
    The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features. (PubMed, J Pathol Clin Res)
    Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    ER positive • HER-2 negative • PIK3CA mutation • PTEN expression • AKT1 mutation • MTOR mutation
    |
    everolimus
    9ms
    Capivasertib: A Novel AKT Inhibitor Approved for Hormone-Receptor-Positive, HER-2-Negative Metastatic Breast Cancer. (PubMed, Ann Pharmacother)
    In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy. Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.
    Review • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
    |
    HR positive • HER-2 negative • PIK3CA mutation • PTEN mutation • AKT1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive
    |
    fulvestrant • Truqap (capivasertib)
    9ms
    The frequency of NRAS mutation in stool samples of Iranian colorectal cancers compared to Finnish patients. (PubMed, J Res Med Sci)
    Mutations in NRAS and FGFR3 were observed only in the Iranian cohort, while APC mutations were exclusive for the Finnish cohort. Genes involved in MAPK and PI3K-MAPK pathways showed a higher frequency of mutations in Iranian patients which may have therapeutic implications.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • STK11 mutation • KIT mutation • APC mutation • AKT1 mutation
    9ms
    Landscape of PIK3CA, PTEN, and AKT1 alterations in advanced breast cancer (ABC) using circulating tumor DNA (ctDNA): Next generation sequencing (NGS) in Asia and the Middle East (AME) (ESMO-BC 2024)
    Conclusions To our knowledge, this is the first AME-specific dataset illustrating that ctDNA NGS can identify PIK3CAm, PTENm, AKT1m, and co-alterations that may inform therapeutic decisions for patients with ABC. Our results indicate a similar prevalence of these mutations in AME and other regions.
    MSi-H Biomarker • Next-generation sequencing • Circulating tumor DNA • Metastases
    |
    ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • GATA1 (GATA Binding Protein 1)
    |
    TP53 mutation • MSI-H/dMMR • PIK3CA mutation • PTEN mutation • AKT1 mutation • PIK3CA E545
    |
    Guardant360® CDx
    9ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
    |
    HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation
    10ms
    Comprehensive molecular and immune profiling of triple negative invasive lobular carcinoma (AACR 2024)
    These data suggest that TN-ILC had higher frequency of CDH1, ERBB2, AKT1, ARID1A mutations, higher M2 macrophages and neutrophils and lower M1 macrophages and CD8 T cells infiltration and, lower T cell inflamed signature. High TMB and AR expression can translate into use of immunotherapy (ICI) and AR antagonists in these patients. Additonal analysis to determine the optimal biomarker for ICI response in TN-ILC is needed.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • BCL2 (B-cell CLL/lymphoma 2) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MCL1 (Myeloid cell leukemia 1) • LAG3 (Lymphocyte Activating 3) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • BCL2A1 (BCL2 Related Protein A1) • FOXP3 (Forkhead Box P3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • BCL2L10 (BCL2 like 10) • BAK1 (BCL2 Antagonist/Killer 1)
    |
    PD-L1 expression • ER positive • TMB-H • MSI-H/dMMR • HER-2 mutation • ARID1A mutation • BCL2 expression • AKT1 mutation • AR expression
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
    10ms
    Genomic Variability Within Intrinsic Subtypes of Advanced Breast Cancer (USCAP 2024)
    There is a great genomic variability in each intrinsic subtype of advanced BC, with apparently no genomic pattern correlating with each phenotype. Although a transcriptomic test (Prosigna) can help in the classification of the tumors, NGS sequencing with an extended panel allows identifying genetic variants that might benefit the patient with a targeted therapy i a significant percentage of cases.
    BRCA Biomarker • Metastases
    |
    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) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)
    |
    HER-2 negative • PTEN mutation • MYC amplification • CCND1 amplification • AKT1 mutation • TP53 amplification
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    10ms
    BMPR1A G298D Point Mutation is a Recurrent Genomic Event in a Subset of Presumably Sex Cord-Stromal Tumors with Ambiguous Features Between Adult and Juvenile Granulosa Cell Tumors (USCAP 2024)
    BMPR1A G298D mutation was exclusively identified in a subset of driverless neoplasms which were classified as granulosa cell tumors (3/27=11%). For BMPR1A-mutant tumors, the overall absence of any detectable known driver mutations supports our hypothesis that this alteration could be an alternative rare tumorigenic mechanism.
    Clinical • Stroma
    |
    AKT1 (V-akt murine thymoma viral oncogene homolog 1) • GNAS (GNAS Complex Locus) • DICER1 (Dicer 1 Ribonuclease III) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • FOXL2 (Forkhead Box L2)
    |
    AKT1 mutation • GNAS mutation
    |
    FoundationOne® CDx
    10ms
    A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma. (PubMed, Cytokine)
    Treatment with the conventional drug of choice AZD5363 (a pan AKT inhibitor) enhanced cell death and diminished HK2 levels in AKT1 mutants...By affecting metabolism, inflammation, and redox homeostasis AKT1-E17K confers a survival advantage in meningioma cells. Our findings suggest that targeting AKT-HK2 cross-talk to induce ROS-dependent cell death could be exploited as novel therapeutic approach in meningiomas.
    Journal
    |
    AKT1 (V-akt murine thymoma viral oncogene homolog 1) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • TLR4 (Toll Like Receptor 4) • HK2 (Hexokinase 2) • IL1B (Interleukin 1, beta) • SOD1 (Superoxide Dismutase 1)
    |
    AKT1 E17K • AKT1 mutation
    |
    Truqap (capivasertib)
    11ms
    Single-cell RNA sequencing reveals the mechanism of PI3K/AKT/mTOR signaling pathway activation in lung adenocarcinoma by KRAS mutation. (PubMed, J Gene Med)
    The present study provides a basic theory for the activation of the PI3K/AKT/mTOR signaling pathway as a result of KRAS mutations.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PDPK1 (3-Phosphoinositide dependent protein kinase 1)
    |
    KRAS mutation • PIK3CA mutation • KRAS wild-type • RAS wild-type • AKT1 mutation • KRAS expression
    |
    Ibrance (palbociclib)
    11ms
    Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study. (PubMed, J Neurosurg)
    These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.
    Clinical • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NF2 (Neurofibromin 2) • KLF4 (Kruppel-like factor 4)
    |
    PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • AKT1 E17K • NF2 mutation • AKT1 mutation • PIK3CA E545 • KLF4 K409Q
    11ms
    Genetic Polymorphisms and Tumoral Mutational Profiles over Survival in Advanced Colorectal Cancer Patients: An Exploratory Study. (PubMed, Curr Oncol)
    Additionally, findings from the genomics of drug sensitivity (GDSC) project demonstrated that cell lines with wild-type BRAF have higher IC50 values for 5-FU compared to BRAF-mutated cell lines. In conclusion, the genetic polymorphisms DPYDrs1801265, ABCB1rs1045642, and MTHFRrs180113 may serve as useful biomarkers for predicting a poor prognosis in patients undergoing 5-fluorouracil chemotherapy, regardless of oncogene mutations.
    Retrospective data • Journal • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • MTHFR (Methylenetetrahydrofolate Reductase) • DPYD (Dihydropyrimidine Dehydrogenase)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • BRAF wild-type • AKT1 mutation
    |
    5-fluorouracil • leucovorin calcium
    11ms
    Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations (YIR 2024)
    Background: PIK3CA mutations occur in ~40% of HR-positive breast cancers, where alpelisib, an orthosteric PI3Kα inhibitor, is FDA-approved in combination with fulvestrant... To identify on-target and off-target alterations potentially mediating resistance to PI3Kα inhibitors, we used a targeted next-generation sequencing assay (Guardant360; Guardant Health) to analyze ctDNA in serially collected plasma samples from 32 patients with PIK3CA-mutated advanced HR-positive, HER2-negative breast cancer treated with alpelisib and inavolisib...Some mutations had differential effects on PI3Kaselective vs. pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Ka-inhibitor RLY-2608... In one of the largest patient cohorts analyzed to date, this study defines the clinical landscape of acquired resistance to PI3Ka inhibitors. Genomic alterations within the PI3K pathway represent a major mode of resistance and identify a novel class of secondary PIK3CA resistance mutations that can be overcome by an allosteric PI3Ka inhibitor. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers.
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HR positive • HER-2 negative • PIK3CA mutation • PIK3CA H1047R • PIK3CA E545K • AKT1 mutation • PIK3CA E545 • PTEN mutation + HR positive
    |
    Guardant360® CDx
    |
    Piqray (alpelisib) • fulvestrant • RLY-2608 • Itovebi (inavolisib)
    11ms
    Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules (clinicaltrials.gov)
    P1, N=285, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    ER positive • PIK3CA mutation • PTEN mutation • AKT1 mutation
    |
    fulvestrant • Truqap (capivasertib)
    11ms
    Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing. (PubMed, Cytotherapy)
    To investigate the basis of this lack of recognition we performed immunopeptidomics analysis of a mutant-overexpressing lymphoblastoid cell line and found that the ESR1 Y537S neopeptide was not endogenously processed, despite binding to HLA-B*40:02 when exogenously pulsed onto the target cell. These results indicate that stimulation of T cells that likely derive from the naïve repertoire with pulsed minimal peptides may lead to the expansion of clones that recognize non-processed peptides, and highlights the importance of using methods that selectively expand T cells with specificity for antigens that are efficiently processed and presented.
    Journal • IO biomarker
    |
    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) • IFNG (Interferon, gamma) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
    |
    TP53 mutation • PIK3CA mutation • ER mutation • ER Y537S • ER D538G • ESR1 mutation • AKT1 mutation
    12ms
    p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane. (PubMed, Br J Cancer)
    This study identified a subset of patients with hormone receptor-positive endocrine-resistant metastatic breast cancer and poor outcome who would derive less benefit from everolimus and exemestane. p4EBP1 may be a useful predictive biomarker in routine clinical practice.
    Journal • Metastases
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    ER positive • HR positive • PIK3CA mutation • PTEN mutation • AKT1 mutation
    |
    everolimus • exemestane
    12ms
    Integrated Molecular Characterization of HER2-Low Breast Cancer Using Next Generation Sequencing (NGS). (PubMed, Biomedicines)
    One case of MSI was detected in a HER2-negative and ISH unamplified case. Beside IHC, NGS allows the identification of HER2-low subtype simultaneously, with the detection of multiple actionable gene mutations being helpful for molecular board treatment selection.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    TP53 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • PIK3CA mutation • AKT1 mutation
    1year
    Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations. (PubMed, Am J Surg Pathol)
    Typical morphologic structures, CK7(+), CK20(-), CDX2(-), p63(-), p40(-), MAML2 fluorescence in situ hybridization (-), AR(-), TTF-1(-), S100(-), mammaglobin(-), or S100/mammaglobin(+) with ETV6 fluorescence in situ hybridization (-) immunophenotype, and recurrent AKT1 E17K or BRAF V600E mutations may be defined. To our knowledge, this small series represents the first genetic study on a typical colloid pattern of MA, and our study with the spectrum documentation for MA in clinicopathologic characteristics, histologic and immunophenotypes, molecular features, and clinical behavior will allow for a better understanding of these rare but distinctive tumors.
    Journal
    |
    BRAF (B-raf proto-oncogene) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ETV6 (ETS Variant Transcription Factor 6) • NKX2-1 (NK2 Homeobox 1) • CDX2 (Caudal Type Homeobox 2) • TP63 (Tumor protein 63) • MAML2 (Mastermind Like Transcriptional Coactivator 2)
    |
    BRAF V600E • BRAF V600 • AKT1 E17K • AKT1 mutation
    1year
    Negative hyperselection of elderly patients with RAS and BRAF wild-type metastatic colorectal cancer receiving initial panitumumab plus FOLFOX or 5-FU/LV. (PubMed, Eur J Cancer)
    Molecular hyperselection and comprehensive genomic profiling have a potential usefulness in elderly patients with RAS/BRAF wild-type, pMMR/MSS mCRC, eligible for upfront EGFR inhibition.
    Journal • Metastases
    |
    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) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • RAS (Rat Sarcoma Virus) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    HER-2 amplification • PIK3CA mutation • MET amplification • PTEN mutation • ALK rearrangement • BRAF wild-type • MET mutation • RET rearrangement • AKT1 mutation • PIK3CA mutation + PTEN mutation • ALK rearrangement + PIK3CA mutation
    |
    5-fluorouracil • Vectibix (panitumumab) • leucovorin calcium
    1year
    Clinical and genomic landscape of FGFR3-altered urothelial carcinoma and treatment outcomes with erdafitinib: a real-world experience. (PubMed, Clin Cancer Res)
    FGFR3 mutations are common in urothelial carcinoma, whereas FGFR2 alterations are rare. Discordance of FGFR3 mutational status between primary and metastatic tumors occurs frequently and raises concern over sequencing archival primary tumors to guide patient selection for erdafitinib therapy. Erdafitinib responses were typically brief and dosing was limited by toxicity. FGFR3, AKT1, and TP53 mutations detected in cfDNA represent putative mechanisms of acquired erdafitinib resistance.
    Journal • Real-world evidence • Real-world
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    TP53 mutation • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • AKT1 mutation • FGFR3 fusion
    |
    Balversa (erdafitinib)
    1year
    Genetic Characterization and Mutational Profiling of Foramen Magnum Meningiomas: A Multi-Institutional Study (SNO 2023)
    Our findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.
    Clinical
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NF2 (Neurofibromin 2) • KLF4 (Kruppel-like factor 4)
    |
    PIK3CA mutation • AKT1 E17K • NF2 mutation • AKT1 mutation
    1year
    Allosteric PI3K-alpha inhibition overcomes on-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations. (PubMed, Cancer Discov)
    PIK3CA mutations occur in ~8% of cancers, including ~40% of HR-positive breast cancers, where the PI3K-alpha (PI3Ka)-selective inhibitor alpelisib is FDA-approved in combination with fulvestrant. Some mutations had differential effects on PI3Ka-selective vs. pan-PI3K inhibitors, but resistance induced by all mutations could be overcome by the novel allosteric pan-mutant-selective PI3Ka-inhibitor RLY-2608. Together, these findings provide insights to guide strategies to overcome resistance in PIK3CA-mutated cancers.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
    |
    HR positive • PIK3CA mutation • AKT1 mutation
    |
    Piqray (alpelisib) • fulvestrant • RLY-2608