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    TEST:
    MI Tumor Seek™

    Company:
    Caris Life Sci
    Type:
    Laboratory Developed Test
    Related tests:
    Details
    Evidence

    News

    5d
    Evidence for Unified Assessment Criteria of HER2 IHC in Colorectal Carcinoma. (PubMed, Mod Pathol)
    Among 22 HER2-positive/heterogenous cases with successful ISH testing, 100% (22/22) demonstrated amplification via ISH. Because the classification of tumors as HER2-positive/heterogenous by IHC correlated very closely with ISH positivity, our results suggest that ISH is likely unnecessary for CRCs with 3+ HER2 overexpression in 10-49% of neoplastic cells.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 positive • HER-2 overexpression • RAS wild-type • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
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    PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • MI Tumor Seek™
    8d
    Detection of Novel Fusion Events in Gastric Carcinoma Involving the ARHGAP Gene Family (AMP 2024)
    Our study documents novel fusions in MSS gastric carcinoma involving the ARHGAP family. Patients with these tumors usually lack eligibility for targeted therapies, such as those directed against HER2 and involving immune checkpoint inhibition, and could ultimately benefit from new treatment avenues modulating RHOA activity as a result of ARHGAP fusions.
    Tumor mutational burden • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • CLDN18 (Claudin 18) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • KDM6A (Lysine Demethylase 6A) • RHOA (Ras homolog family member A) • SOX9 (SRY-Box Transcription Factor 9) • ELF3 (E74 Like ETS Transcription Factor 3) • ARHGAP • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CTNND1 (Catenin Delta 1) • ARHGAP42 (Rho GTPase Activating Protein 42)
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    TMB-H • HER-2 amplification • PBRM1 mutation
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    MI Tumor Seek™
    14d
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
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    MI Tumor Seek™
    2ms
    Identifying regulators of MHC repression and therapeutic targets to overcome immune evasion in SCLC (SITC 2024)
    Moreover, our study identifies the direct role of DNAPKCs as a therapeutic target that can augment the anti-tumor immune response of PD-L1-blockade by induction of MHC-I expression in SCLC. Our findings have important implications for harnessing NHEJ regulators for immunotherapy in SCLC, a cancer in critical need of better therapeutic options.
    PD(L)-1 Biomarker • IO biomarker
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    HLA-A (Major Histocompatibility Complex, Class I, A) • HLA-B (Major Histocompatibility Complex, Class I, B) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • TAP1 (Transporter 1) • HLA-C (Major Histocompatibility Complex, Class I, C)
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    MI Tumor Seek™
    2ms
    Identifying regulators of MHC repression and therapeutic targets to overcome immune evasion in SCLC (SITC 2024)
    Moreover, our study identifies the direct role of DNAPKCs as a therapeutic target that can augment the anti-tumor immune response of PD-L1-blockade by induction of MHC-I expression in SCLC. Our findings have important implications for harnessing NHEJ regulators for immunotherapy in SCLC, a cancer in critical need of better therapeutic options.
    PD(L)-1 Biomarker • IO biomarker
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    HLA-A (Major Histocompatibility Complex, Class I, A) • HLA-B (Major Histocompatibility Complex, Class I, B) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • TAP1 (Transporter 1) • HLA-C (Major Histocompatibility Complex, Class I, C)
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    MI Tumor Seek™
    2ms
    Identifying Regulators of MHC Repression and therapeutic targets to overcome immune evasion in SCLC. (EORTC-NCI-AACR 2024)
    We provide novel insight into the mechanisms of SCLC immunotherapy resistance and MHC repression. We established the heterogeneity of MHC repression across SCLC tumors and identified networks and pathways that can be targeted to de-repress MHC-I in SCLC. Moreover, we identified the direct role of DNAPKCs as a therapeutic target that can augment the anti-tumor immune response of PD-L1 blockade by induction of MHC-I expression in SCLC.
    PD(L)-1 Biomarker • IO biomarker
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    HLA-A (Major Histocompatibility Complex, Class I, A) • HLA-B (Major Histocompatibility Complex, Class I, B) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • TAP1 (Transporter 1) • HLA-C (Major Histocompatibility Complex, Class I, C)
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    MI Tumor Seek™
    2ms
    Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology. (PubMed, Lung Cancer)
    METex14+ alterations are a heterogeneous subgroup of NSCLC. Our analysis reveals that METex14+ nSq exhibit improved survival compared to METex14+ Sq. The distinct genomic and transcriptomic variations across histologies warrant clinical consideration.
    Journal • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • CD8 (cluster of differentiation 8) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • HMGA2 (High mobility group AT-hook 2) • POT1 (Protection of telomeres 1)
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    TP53 mutation • TMB-H • MET exon 14 mutation • STK11 mutation • KEAP1 mutation • POT1 mutation
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    3ms
    Androgen production, uptake, and conversion (APUC) genes define prostate cancer patients with distinct clinical outcomes. (PubMed, JCI Insight)
    The APUC-6 high/AR-low tumors represented a subgroup of patients with good clinical outcomes in contrast to the AR-high or neuroendocrine prostate cancers. Altogether, measuring the aggregate expression of APUC-6 genes in current genomic tests identifies PCs that are ligand- (rather than AR-) driven and require distinct therapeutic strategies.
    Journal • Clinical data
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    ER (Estrogen receptor) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • CYP11B1 (Cytochrome P450 Family 11 Subfamily B Member 1) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • HSD3B1 (Hydroxy-Delta-5-Steroid Dehydrogenase 3 Beta- And Steroid Delta-Isomerase 1)
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    MI Tumor Seek™
    4ms
    HER3 Expression Across Genomic Subsets of NSCLC (IASLC-WCLC 2024)
    High ERBB3 expression was associated with better survival. These data support the role of HER3 as a viable therapeutic target across multiple molecular subsets.
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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    KRAS mutation • EGFR mutation • KRAS G12C • EGFR L858R • HER-2 expression • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR expression • MET exon 14 mutation • ALK fusion • ERBB3 expression • ROS1 fusion • KRAS G12 • EGFR exon 20 mutation • ERBB3 mutation • KRAS expression
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    MI Tumor Seek™
    4ms
    Molecular and immunologic correlates of high PSMA/FOLH1 mRNA expression in prostate cancer (PC) (ESMO 2024)
    This is the largest combined clinicogenomic analysis of FOLH1 expression in PC. Tumors with high FOLH1 are molecularly and immunologically distinct, providing insights for distinct therapeutic strategies in this group.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AR (Androgen receptor) • ASXL1 (ASXL Transcriptional Regulator 1) • LAG3 (Lymphocyte Activating 3) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • FOLH1 (Folate hydrolase 1) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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    PD-L1 expression • LAG3 expression • AR splice variant 7 • FOLH1 expression • FOLH1 overexpression • PD-L2 expression
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    4ms
    Impact of TLS status on outcomes in patients with high TMB or MSI-high status treated with immune checkpoint inhibitors (ESMO 2024)
    High TLS gene expression signatures, particularly in the highest quartile, are associated with favorable outcomes in patients with high TMB or MSI-High status treated with pembrolizumab. These findings suggest that TLS status could serve as a potent biomarker to stratify patients more likely to benefit from ICI therapy, advocating for its integration into routine clinical assessments prior to ICI treatment in these specific group of patients.
    Clinical • Checkpoint inhibition • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
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    PD-L1 expression • TMB-H • MSI-H/dMMR • TLS gene signature
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay • PD-L1 IHC 28-8 pharmDx • MI Tumor Seek™
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    Keytruda (pembrolizumab)
    4ms
    Genomic landscape and prognostic impact of HER2 low-expressing tumors (ESMO 2024)
    Significant associations between ERBB2 alterations and HER2 low-expressing tumors were observed. High prevalence of ERBB2 alterations was observed in some uncommonly tested tumors. Median OS of HER2 low-expressors was better than non-expressors in this heterogenous group.
    HER-2 (Human epidermal growth factor receptor 2)
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    HER-2 amplification • HER-2 mutation • HER-2 expression • HER-2 underexpression
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    MI Tumor Seek™
    4ms
    Atlas of tertiary lymphoid structures in solid tumors: Genomic features and prediction of response to immunotherapy (ESMO 2024)
    We assessed gene signatures indicative of B cell infiltration/TLS presence (Messina et al., 2012; Goc et al., 2014; Cabrita et al., 2020; Meylan, et al., 2022), correlating these with clinical outcomes, including overall survival (OS) and time on treatment (TOT) for ICIs such as pembrolizumab, nivolumab, and ipilimumab. This large TLS atlas based on real-world data demonstrate that TLS gene is a robust biomarker for predicting responses to immunotherapy in solid tumors.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • APC (APC Regulator Of WNT Signaling Pathway)
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    KRAS mutation • EGFR mutation • STK11 mutation • KEAP1 mutation • APC mutation • TLS gene signature
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    MI Tumor Seek™
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    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab)
    4ms
    Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial. (PubMed, Eur Urol)
    P2; Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC). We conclude that this biomarker test, when combined with careful clinical assessment, can be used to allocate patients to careful bladder surveillance instead of surgery. This hypothesis has been tested in the RETAIN trial presented previously (NCT02710734).
    Journal
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    ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • ERCC2 (Excision repair cross-complementation group 2) • FANCC (FA Complementation Group C)
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    MI Tumor Seek™
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    cisplatin • gemcitabine • doxorubicin hydrochloride • methotrexate • vinblastine
    7ms
    Pan-Cancer Interrogation of B7-H3 (CD276) as an Actionable Therapeutic Target across Human Malignancies. (PubMed, Cancer Res Commun)
    We have begun to define the genomic, transcriptomic, clinical, and immunological features associated with B7-H3 expression in 50 cancer types. We report novel clinical and molecular features of B7-H3-high tumors which may inform how current B7-H3 therapeutics should be deployed and prioritized.
    Journal • Pan tumor
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8) • CD276 (CD276 Molecule) • TGFB1 (Transforming Growth Factor Beta 1)
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    CD276 expression • TP53 expression
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    MI Tumor Seek™
    7ms
    Young lung adenocarcinoma: Molecular analysis pointing to early acquisition of aggressive mutations. (ASCO 2024)
    We identified a high prevalence of KRAS G12C, previously associated with increasing age and environmental insults, and EGFR exon 21 L858R in a YA population. Alterations in HHR genes and TP53 were present at high rates. Acquisition of aggressive forms of KRAS and EGFR mutation, as well as the high prevalence of TP53 and HHR defects, may contribute to early disease development.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • HRD (Homologous Recombination Deficiency)
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    MI Tumor Seek™
    7ms
    Immune checkpoint inhibitor treatment in PD-L1-negative gastroesophageal cancer tumors. (ASCO 2024)
    CD274-H trended towards worse post-Carboplatin/paclitaxel (CP) OS (ES: 13. High CD274 expression was associated with improved survival when Nivolumab was added to chemotherapy in patients with PD-L1-negative tumors. Further investigation is needed to confirm the potential benefits of Nivolumab treatment in gastroesophageal cancer patients with tumors that are PD-L1-negative by IHC but exhibit high mRNA expression.
    Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
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    Opdivo (nivolumab) • carboplatin • paclitaxel
    7ms
    The impact of metformin on clinical outcomes of metastatic colorectal cancer with known molecular profile treated with cytotoxic chemotherapy or immune checkpoint inhibitor. (ASCO 2024)
    In this retrospective analysis of real-world clinical outcomes, patients receiving concomitant metformin and cytotoxic chemotherapy had improved clinical outcomes in MSS CRC compared to those not on concurrent metformin. However, the concurrent use of metformin with ICIs in MSI-H CRC did not show an impact on clinical outcomes given low sample size. These results add to the existing body of literature on the potential benefits of metformin in the context of MSS CRC and underscore the importance of a prospective controlled study of concurrent metformin use with systemic chemotherapy in metastatic CRC.
    Checkpoint inhibition • Clinical data • Clinical • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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    MI Tumor Seek™
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    metformin
    7ms
    The role of the ubiquitin ligase UBE4B in neural tumors in adults and children. (ASCO 2024)
    Higher UBE4B expression in younger GBM cases correlated with improved OS suggesting it may have utility as a prognostic biomarker. Increased expression of GFRs in younger patients with high UBE4B expression may provide rationale for new treatment strategies in these patients. Future work may prioritize designing drug targets for UBE4B, offering therapeutic opportunities, especially for younger GBM patients.
    Clinical • IO biomarker
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    EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • IFNG (Interferon, gamma)
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    MI Tumor Seek™
    7ms
    Real-world impact of KRAS mutations on clinical outcomes in metastatic colorectal cancer treated with trifluridine-tipiracil in the USA. (ASCO 2024)
    To our knowledge, this is the largest primarily US-based cohort of mCRC treated with FTD-TPI to be reported. KRAS G12 mutation, but not KRAS G13 mutation, was associated with shorter rwOS and ToT compared to KRAS WT, despite enrichment of TP53 and BRAF mutations in the KRAS WT group. This finding is consistent with previously published analyses of large randomized prospective trials of FTD-TPI in mCRC and further support KRAS mutation status as a predictive biomarker in this setting.
    Real-world evidence • Clinical data • Clinical • Real-world • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53)
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    MI Tumor Seek™
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    Lonsurf (trifluridine/tipiracil)
    7ms
    Genomic and immune profiling of rare non-squamous sinonasal tumors. (ASCO 2024)
    To our knowledge, this is the largest study characterizing the genomic and immune alterations in non-squamous SNTs. Our findings offer potential for future targeted and immune therapeutic applications in these rare diseases.
    PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD4 (CD4 Molecule)
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    7ms
    Characterization of enhancer of zeste homolog 2 (EZH2) expression, activity, and association with the tumor immune microenvironment in olfactory neuroblastoma (ONB). (ASCO 2024)
    EZH2 mutations were not detected in ONB or ES, though similar EZH2 activity (by ERS) was observed in both cohorts, thus making ONB an intriguing candidate for EZH2 modulating therapies. High ERS in ONB was associated with expression of immune checkpoint genes suggesting that inhibiting EZH2 activity could enhance the susceptibility of ONB to immune checkpoint blockade.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • PD-1 (Programmed cell death 1)
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    7ms
    Racial differences in genomic profiles and clinical outcomes of patients with colorectal carcinoma: A single institution retrospective study. (ASCO 2024)
    White and black CRC patients have unique molecular tumor profiles that may better explain the differences in survival. Our results warrant larger studies with racially and ethnically diverse patient populations to explore these racial disparities and close the gap in colorectal cancer care.
    Clinical data • Retrospective data
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7)
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    MI Tumor Seek™
    7ms
    RNA expression-based hypoxia score as a prognostic and predictive biomarker in hepatocellular carcinoma. (ASCO 2024)
    Yet, no significant difference in survival since start of treatment (SSOT) was observed in the patient subset that received Atezolizumab (Atezo) (-H: 210 D, -M: 355 D, -L: 386 D, p= 0.54). In HS-M tumors alone, SSOT was similar across investigated therapeutics (Atezo 322 D, Lenvatinib (Lenvat) 366.5 D, Sorafenib (Soraf) 289 D, p= 0.34)... In HCC, RNA expression-based HS is associated with TP53 mutations and an immunosuppressive microenvironment. HS-H tumors has worse OS that may be improved with Atezo, whereas HS-L tumors may respond better to Soraf. HS is a potential prognostic and predictive biomarker in HCC that deserves validation in orthogonal data sets and prospective studies.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53)
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    Tecentriq (atezolizumab) • sorafenib • Lenvima (lenvatinib)
    7ms
    Molecular landscape and site of metastasis in PDAC. (ASCO 2024)
    This association held for tumors treated with Immune Checkpoint Inhibitors (ICI) (9.6 m vs 4.6 m, HR=0.71 95% CI: 0.52-0.97, p=0.031), Gemcitabine/Nab-paclitaxel treated (15.3 m vs 8.1 m, HR=0.57 95% CI: 0.52-0.61, p<0.001) as well as mFOLFIRINOX treated tumors (20.3 m vs 12.0 m, HR=0.57 95% CI: 0.52-0.63, p<0.001). When comparing pancreatic LM to OM sites, our data reinforces the observation that OS is better in OM vs LM and response to ICI was better in OM vs. LM. Significant differences were observed in molecular landscape, TME and signatures that are predictive of immunotherapy response (TIS and IFG scores).
    MSi-H Biomarker • BRCA Biomarker • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • IFNG (Interferon, gamma) • RNF43 (Ring Finger Protein 43) • KDM6A (Lysine Demethylase 6A) • GNAS (GNAS Complex Locus)
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    MI Tumor Seek™
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    gemcitabine • albumin-bound paclitaxel • irinotecan
    7ms
    Unlocking therapeutic potential: IL-1β as a target in non-small cell lung cancer with oncogenic mutations—Prognostic and predictive insights. (ASCO 2024)
    The phase II CANTOS trial incidentally showed reduced lung cancer incidence and mortality with the IL-1β inhibitor canakinumab... Our study shows promising prognostic value of IL-1β expression in NSCLC, associating low expression with improved OS across NSCLC subtypes. IL-1β expression is closely linked to key driver mutations in NSCLC and may have predictive value for ICIs. The findings suggest the potential benefit of targeting IL-1β in high IL-1β expressing NSCLC with driver mutations.
    PD(L)-1 Biomarker • IO biomarker
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    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) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • IL1B (Interleukin 1, beta)
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    MI Tumor Seek™
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    Ilaris (canakinumab)
    7ms
    The molecular landscape of PIWIL1 expression in colorectal adenocarcinoma (CRC). (ASCO 2024)
    PIWIL1-H CRC is associated with higher rates of dMMR/MSI-H, TMB-H and PD-L1+ as well as IO-related gene expression and signatures that are predictive of response to IO. These data suggest the PIWIL1-H subpopulation could potentially derive substantial benefit from PIWIL1-targeted immunotherapy which should be evaluated in clinical trials.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule)
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    7ms
    Uncovering actionable genetic alterations and immune predictive biomarkers for anal squamous cell carcinomas in the era of immunotherapy: PD-L1 and beyond. (ASCO 2024)
    PD-L1 is expressed in over 50% of SCACs, while dMMR/MSI-H is rare. High PD-L1-expressing tumors have higher PIK3CAand CASP8 mutations and overexpress IO markers, are inflamed, and have prolonged treatment times with ICIs. This is the largest study to date reporting SCAC genomic profiles and identifies the utility of PD-L1 as a predictive biomarker of IO efficacy.
    Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • BAP1 (BRCA1 Associated Protein 1) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • PD-L2 (Programmed Cell Death 1 Ligand 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CASP8 (Caspase 8) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    7ms
    Molecular and immunological characterization of androgen receptor expression in different breast cancer subtypes. (ASCO 2024)
    Post-doxorubicin survival was longer for patients with AR-H tumors; however, opposing trends were observed for patients with LumB (75.5 vs 56.3 m; p=.081) and HER2-enriched tumors (47.9 vs 65.2 m; p.071)... Findings from our updated analysis based on PAM50 designation suggest a strong association between AR and PIK3CA mutations across subtypes and suggest that distinct AR-associated alterations in the immune microenvironment require further study. Exploration of specific mutations and immune-oncology markers associated with AR-H may aid in molecularly selected clinical trial design for advanced BC patients.
    PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • AR (Androgen receptor) • NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • CDH1 (Cadherin 1) • CD4 (CD4 Molecule) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
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    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MI Tumor Seek™
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    doxorubicin hydrochloride
    7ms
    Characterization of necroptosis activators in colorectal cancer. (ASCO 2024)
    NA-H showed significantly improved OS in FOLFOX/FOLFIRI (F/F) (NA-L: 34.3 vs NA-H: 39.6 months [mo], P< 0.001; HR = 0.83, 95% CI 0.77 – 0.90) and those treated with IO (15.3 vs 22.4 mo, P = 0.018; HR = 0.77, 95% CI 0.62– 0.96) treated CRC patients... This is the largest molecular and clinical characterization of necroptotic genes in CRC. Our data shows that activation of the necroptosis pathway is associated with immune cell infiltration/pathway activation, PD-L1 expression, and improved OS on F/F and IO. This benefit is more pronounced in TP53-mutated CRC, suggesting possible novel therapeutic targets.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IFNG (Interferon, gamma) • SMAD4 (SMAD family member 4) • IGF2BP1 (Insulin Like Growth Factor 2 MRNA Binding Protein 1) • SMAD2 (SMAD Family Member 2)
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
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    5-fluorouracil • irinotecan • leucovorin calcium
    7ms
    Kinome reprogramming as a therapeutic opportunity in ESR1 fusion driven breast cancer but not in gynecologic cancers. (ASCO 2024)
    We highlight that ESR1fusions can be reliably detected in patients with breast cancer, ovarian cancer, and endometrial cancers. ESR1 fusions lose the ligand binding domain and cannot be targeted using current estrogen modulators or degraders. We have discovered the upregulation of oncogenic kinase signaling in ESR1 fusion positive breast cancer, but not in gynecologic cancers.
    ER (Estrogen receptor) • TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • FOXA1 (Forkhead Box A1)
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    MI Tumor Seek™
    7ms
    Genomic and tumor microenvironment dynamics of brain metastases in breast cancer. (ASCO 2024)
    BM in BC are more frequently associated with TNBC and Basal-like BC phenotypes than ECM or PTs. BM have a higher proportion of ESR1-mut than PTs, highlighting a possible association between endocrine resistance and development of BM. BM had lower IFN score and PDL-1 expression highlighting an immunosuppressed tumor microenvironment.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • GATA3 (GATA binding protein 3)
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    VENTANA PD-L1 (SP142) Assay • Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MI Tumor Seek™
    7ms
    The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in small-cell lung cancer (SCLC). (ASCO 2024)
    Increased B cell, M1 and M2 macrophage infiltrates, and increased prevalence of T-cell inflamed tumors in ANTXR1 H TME suggest that these patients with SCLC may respond preferentially to ICI. A Phase 1 trial incorporating SVV-01 along with ICI is underway. Prospective investigation of molecular associations and clinical outcomes related to ANTXR1 expression in SCLC is warranted.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • ANTXR1 (ANTXR Cell Adhesion Molecule 1)
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
    7ms
    Clinical and molecular characterization of AXL in colorectal cancer: CALGB (Alliance)/SWOG 80405 and real-world data. (ASCO 2024)
    Data from the phase III CALGB/SWOG 80405 trial on 433 metastatic CRC (mCRC) patients treated with bevacizumab (Bev, n = 226) or cetuximab (Cet, n = 207) in combination with first-line chemotherapy were also evaluated...AXL-H demonstrated worse OS in FOLFOX/FOLFIRI treated CRC (H: 35.7 vs L: 38.7 months [mo], P = .003; HR 1.08, 95% CI [1.03-1.14])... Our results indicate increased AXL expression is associated with immune cell infiltration, EMT, and inflammatory signaling. AXL-H confers worse OS/PFS on first-line chemotherapy, with a more pronounced effect in KRASwt CRC. This data supports evaluation of AXL as a prognostic marker and potential therapeutic target in CRC.
    Real-world evidence • Clinical • PD(L)-1 Biomarker • IO biomarker • Real-world
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • AXL (AXL Receptor Tyrosine Kinase) • IFNG (Interferon, gamma) • RNF43 (Ring Finger Protein 43) • TNFA (Tumor Necrosis Factor-Alpha)
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
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    Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • irinotecan • leucovorin calcium
    7ms
    Molecular and immune characterization of squamous cell ovarian cancers for identification of therapeutic targets. (ASCO 2024)
    OSCC had worse post-Carboplatin survival (19.6 mo) compared to EOC (71.6 mo, p<0.01) and CCOC (46.9 mo, p<0.01), similar post-Carbo survival to TP53-mt CSCC (22.5 mo; p=0.80) but improved post-Carbo survival compared to TP53-mt VSCC (9.05 mo; p=0.01)... The molecular and transcriptomic profile of OSCC is distinct from EOC, CCOC, and BT but similar to CSCC and VSCC. OSCC demonstrated a more immune hot phenotype. Further studies are needed to investigate the potential use of immunotherapy in OSCC.
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • IFNG (Interferon, gamma) • KMT2D (Lysine Methyltransferase 2D) • TNFA (Tumor Necrosis Factor-Alpha)
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    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    carboplatin
    7ms
    Molecular and clinical correlates of high PSMA/FOLH1 mRNA expression in primary and metastatic prostate cancer (PC). (ASCO 2024)
    This is the largest combined genomic, transcriptomic and survival outcomes analysis of PSMA (FOLH1) expression in PC. In PC, greater FOLH1 mRNA expression was associated with higher AR signaling scores and AR-V7 expression, and fewer mutations in the Wnt and PI3K pathways. FOLH1-high pts showed greater T cell inflammation and PD-L1 expression, and lower NEPC signaling.
    Clinical • PD(L)-1 Biomarker • PARP Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ASXL1 (ASXL Transcriptional Regulator 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • FOLH1 (Folate hydrolase 1)
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
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    Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
    7ms
    Dissecting the significance of ACP1 gene alterations in prostate cancer (PCa). (ASCO 2024)
    In the largest study investigating the significance of ACP1 expression in PCa, we demonstrate that ACP1-high tumors exhibit a distinct molecular profile enriched for TP53 alterations and associated with a 'cold' TME. Our findings may provide a rationale for novel therapeutic targeting of ACP1-high tumors.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TNFA (Tumor Necrosis Factor-Alpha)
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    VENTANA PD-L1 (SP142) Assay • MI Tumor Seek™
    7ms
    Characterization of ESR1 mutations in endometrial and ovarian cancers. (ASCO 2024)
    ESR1mt were more common in EC and were enriched in the endometrioid subtype, and in general associated with increased molecular alterations but a more cold immune microenvironment. Hotspot mutations known to confer endocrine resistance were most common and enrichment was observed in cases previously exposed to AIs, suggesting this may be a mechanism of resistance to endocrine therapy for some gynecologic malignancies.
    Tumor mutational burden
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    ER (Estrogen receptor) • TMB (Tumor Mutational Burden) • ARID1A (AT-rich interaction domain 1A) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)
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    MI Tumor Seek™
    7ms
    Characterizing FOLR1 expression in low-grade serous ovarian carcinoma. (ASCO 2024)
    Amongst tumors that had not received mirvetuximab soravtansine, no difference in OS was observed between HG F- v HG F+ (HR 1.3, p = .072; median OS HG F-: 87 months [N = 1092], HG F+: 98 [N = 756])... A notable portion of LG tumors were FOLR1+, which suggests that FOLR1 expression in LG could be a viable target for this rare histology, particularly in the recurrent setting. MAPK activation was significantly higher in LG tumors when compared to HG, yet no difference between LG F+ and F- tumors was observed.
    PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FOLR1 ( Folate receptor alpha )
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™
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    Elahere (mirvetuximab soravtansine-gynx)
    7ms
    The molecular landscape of pembrolizumab and lenvatinib treatment in endometrial cancer. (ASCO 2024)
    Among POLE-wt/MSS patients, TP53 wild type patients have longer OS after pembrolizumab with lenvatinib compared to pembrolizumab alone, but in the TP53 mutated cohort, there was no difference. Among TP53-mt patients, ARID1A-mt is associated with improved pembro-lenv survival but not in pembro alone. Our findings suggest a need to readdress when to use lenvatinib in TP53-mt patients and further explore genomic alterations that may promote treatment response to optimize use of this agent in endometrial cancer.
    PD(L)-1 Biomarker • MSi-H Biomarker
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    TP53 (Tumor protein P53) • MSI (Microsatellite instability) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A)
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    MI Tumor Seek™
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    Keytruda (pembrolizumab) • Lenvima (lenvatinib)
    7ms
    Survival and mutational differences based on ESR1 and ESR2 expression in non-small cell lung cancer (NSCLC). (ASCO 2024)
    In EGFR-Mt, a significant difference in survival since treatment (SST) with osimertinib was seen for ESR1-L/ESR2-H (40 m, N = 13), ESR1-H/ESR2-L (36 m, N = 62), ESR1-H/ESR2-H (34 m, N = 161) and ESR1-L/ESR2-L (30 m, N = 138, p = .03). In KRAS G12C-Mt, a significant difference in SST was seen with sotorasib; ESR1-H/ESR2-H had the longest SST (median not reached, N = 17), followed by ESR1-H/ESR2-L (17 m, N = 17), ESR1-L/ESR2-L (13 m, N = 34) and ESR1-L/ESR2-H (1 m, N = 1, p = .002)...ESR1-H had a higher percentage of females, AD, and EGFR/KRAS-mt v ESR1-L while ESR2-H had no sex difference, more SCC, and fewer EGFR/KRAS-mt v ESR2-L. ESR1-H/ESR2-H tumors had the highest MPAS and longest OS and there were SST differences with EGFR and KRAS G12C inhibition. ESR1&2 may play key roles in activating the MAPK pathway and future trials could consider targeted therapy combined with ER inhibition based on ESR1&2 expression.
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor)
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    MI Tumor Seek™
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    Tagrisso (osimertinib) • Lumakras (sotorasib)
    7ms
    Multi-omic analysis of the prognostic and predictive value of LAG3 expression in urothelial carcinoma. (ASCO 2024)
    Tumor microenvironment (TME) cell fractions were estimated by RNA deconvolution using quanTIseq. Significance was tested using Mann-Whitney U and
    Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Omic analysis
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • LAG3 (Lymphocyte Activating 3)
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    PD-L1 IHC 22C3 pharmDx • MI Tumor Seek™