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    BIOMARKER:

    TMB-H

    i
    Other names: TMB | Tumor Mutational Burden
    Related biomarkers:
    Expression
    Others
    Related tests:
    1d
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1d
    Durvalumab plus cisplatin and gemcitabine as first line therapy for advanced biliary tract carcinoma (aBTC): a monocentric retrospective experience (AIOM 2024)
    The data presented in this study are consistent with the results of TOPAZ1 trial. However about a third of patients do not respond to CHT or have a short response duration. In our experience both NLR and basal elevated AST/ALT seem to be associated with an improved mPFS and a better outcome but further studies are needed.
    Retrospective data • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
    |
    TP53 mutation • KRAS mutation • TMB-H • TMB-L
    |
    TruSight Oncology 500 Assay
    |
    cisplatin • Imfinzi (durvalumab) • gemcitabine
    1d
    Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (AIOM 2024)
    The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations.
    Clinical • Tumor mutational burden • Circulating tumor DNA • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • PTPRT (Protein tyrosine phosphatase receptor type T)
    |
    KRAS mutation • TMB-H • MET overexpression • PTPRT mutation
    |
    GuardantINFINITY™
    |
    telisotuzumab adizutecan (ABBV-400) • telisotuzumab (h224G11)
    1d
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
    Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    TMB-H • MSI-H/dMMR
    |
    TruSight Oncology 500 Assay
    |
    oxaliplatin • irinotecan
    1d
    A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade. (PubMed, J Cancer Res Clin Oncol)
    We propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.
    Preclinical • Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker • Checkpoint block
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • MSH2 (MutS Homolog 2)
    |
    TMB-H
    2d
    Integrated profile of tumor stage and mutational burden predicts disparate clinical responses to immune checkpoint inhibitors: A risk-benefit study. (PubMed, Semin Oncol)
    This may require enrolling patients with less-severe or early-stage disease to enable long-term follow-up with effective clinical surveillance. By comprehensively evaluating the added benefit of improved treatment efficacy and the potential risk of adverse treatment outcome, a risk-benefit profile can optimize immunotherapy regimens, with profound implications for clinical decision-making and regulatory approvals of ICI.
    Journal • Checkpoint inhibition • Benefit-risk assessment • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L
    3d
    Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration Resistant Prostate Cancer. (PubMed, Clin Cancer Res)
    D+T is active in mCRPC but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.
    P2 data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
    |
    TMB-H • PD-L1 overexpression
    |
    Imfinzi (durvalumab) • Xtandi (enzalutamide capsule) • Imjudo (tremelimumab) • abiraterone acetate
    3d
    KEYNOTE-E64: Phase 1a and Phase 2 Study for Safety, Preliminary Efficacy, PK and PD of ST-067 (clinicaltrials.gov)
    P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025
    Enrollment open • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR • ALK positive • ALK mutation
    |
    Keytruda (pembrolizumab) • Gazyva (obinutuzumab) • vevoctadekin (ST-067)
    5d
    Genomic Landscape of Fusions in Solid Tumors Detected by DNA and RNA Comprehensive Genomic Profiling at a Large Community Health System (AMP 2024)
    The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.
    Tumor mutational burden
    |
    ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion
    |
    TruSight Oncology 500 Assay
    5d
    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
    |
    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)
    |
    TMB-H • HER-2 amplification • PBRM1 mutation
    |
    MI Tumor Seek™
    5d
    Evaluation of Ancestry-Associated Bias in Tumor Mutational Burden Calculation in the TruSight Oncology 500 Platform (AMP 2024)
    Because no significant bias was identified in this limited cohort, an ancestry-based calibration constant or normalization procedure cannot be systematically applied. However, the TMB calling algorithm used by TSO500 relies upon population databases. Therefore, the underlying variants and calculations used to determine TMB should be manually evaluated on a case-by-case basis, particularly for tumors with TMBs close to treatment thresholds in patients of ancestries underrepresented in population databases.
    Tumor mutational burden • IO Companion diagnostic • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    5d
    Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)
    Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.
    Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion
    |
    OncoExTra™ test
    5d
    Comprehensive Genomic and Immune Profiling for the Detection of Clinically Significant Tumor Biomarkers (AMP 2024)
    Utilization of a multi-modal CGIP testing strategy resulted in a high rate of test success and detection of clinically relevant biomarkers and optimizing tissue usage.
    Clinical • Tumor mutational burden • IO Companion diagnostic • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    PD-L1 expression • TMB-H
    |
    TruSight Oncology 500 Assay • Oncomine™ Immune Response Research Assay
    11d
    Current status of cancer genomic profiling (CGP) tests in brain tumor treatment - complementing brain tumor pathological diagnosis with CGP- (SNO 2024)
    Molecular diagnostics through CGP testing served as an aid in diagnosis according to WHO2021. Cases where drug suggestions were feasible underwent treatment with targeted molecular therapies and checkpoint inhibitor. We experienced cases where hereditary cancer syndromes such as Lynch syndrome were diagnosed through the detection of germline pathogenic variants.
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MSH6 (MutS homolog 6)
    |
    BRAF V600E • TMB-H • BRAF V600 • IDH1 R132H • TERT mutation • IDH wild-type • IDH1 R132 • IDH mutation + BRAF V600E
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    12d
    KRAS mutations in endometrial cancers: Possible prognostic and treatment implications. (PubMed, Gynecol Oncol)
    KRAS-mut represents a genotypically distinct group of ECs. Overlap exists with genomic predictors (TMB-high, MSI-high) of immunotherapy response, suggesting a possible biomarker-driven combination option with immunotherapy. Clinical trials to evaluate these strategies should be developed.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)
    |
    KRAS mutation • BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • KRAS G12D • KRAS G12V • KRAS wild-type • KRAS overexpression • HER-2 positive + RAS wild-type
    14d
    Construction of a novel tumor mutation burden-related mRNA signature for prognosis prediction in laryngeal squamous cell carcinoma. (PubMed, Medicine (Baltimore))
    ANKLE1 was negatively related to many drug sensitivities, while PPP1R14A was positively related to some drug sensitivities. We constructed an effective risk model constructed by ANKLE1 and PPP1R14A which was related to TMB in LSCC.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    14d
    Association of tumour mutation burden with prognosis and its clinical significance in stage III gastric cancer. (PubMed, Bioimpacts)
    Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    KRAS mutation • TMB-H • TMB-L
    14d
    Identification and characterization of ADAR1 mutations and changes in gene expression in human cancers. (PubMed, Cancer Genet)
    We also identified several samples with high mutation burden between ADAR1 and other genes regulated primarily in endometrial cancers. Finally, we show that the deaminase domain is highly conserved in metazoans and mutations within conserved residues do occur in human cancers suggesting that destabilization of the enzyme function is contributing to cancer development.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ADAR (Adenosine Deaminase RNA Specific) • BLCAP (BLCAP Apoptosis Inducing Factor)
    |
    TMB-H • PTEN mutation
    17d
    Neurofibroma-like Desmoplastic Melanoma: A Series of Five Cases Exploring the Role of Molecular Testing as a Diagnostic Adjunct and Highlighting the Differential Diagnosis With Diffuse-type Neurofibroma. (PubMed, Am J Surg Pathol)
    Any deviation from the expected clinical or morphologic features of cutaneous diffuse-type neurofibroma should raise suspicion for NFLDM. Although not entirely sensitive or specific, molecular testing can help to support the diagnosis of NFLDM by demonstrating genetic abnormalities associated with melanoma, including a UV-light-induced mutational signature, high tumor mutational burden, and/or chromosomal copy number alterations typical of melanoma.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    17d
    Anti-PD-1 immunotherapy for the treatment of metastatic urothelial carcinoma in a kidney transplant recipient: a case report. (PubMed, BMC Nephrol)
    This case demonstrates the feasibility of safely achieving stable cancer control in a kidney transplant patient with mUC without encountering graft rejection by using single-agent anti-PD-1 treatment.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Tevimbra (tislelizumab-jsgr)
    18d
    The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project. (PubMed, Br J Cancer)
    The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients.
    Journal
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    19d
    Clinical Outcomes of Patients with Colorectal Cancer Who Underwent Comprehensive Genomic Profiling: A Single-institution Non-comparative Prospective Observational Study. (PubMed, J Anus Rectum Colon)
    In Japan, patients with this subtype cannot undergo pembrolizumab without testing for CGP. This prospective observational study's findings provide an overview of CGP testing outcomes in patients with refractory mCRC.
    Clinical data • Observational data • Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H
    |
    Keytruda (pembrolizumab)
    20d
    PD-1 inhibitor sintilimab treated patients with metastatic triple-negative breast cancer. (PubMed, Front Cell Dev Biol)
    In our study, preliminary evidence provided the anticancer activity and acceptable adverse effects of sintilimab administered every 3 weeks to pretreated patients with mTNBC. Sintilimab showed its efficacy and safety of immunotherapy for patients with advanced TNBC.
    Journal • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
    |
    PD-L1 expression • TMB-H
    |
    Tyvyt (sintilimab)
    21d
    Prognostic value of a lactate metabolism gene signature in lung adenocarcinoma and its associations with immune checkpoint blockade therapy response. (PubMed, Medicine (Baltimore))
    Similarly, most immune checkpoint molecules, immune inhibitors/stimulators, and major histocompatibility complex (MHC) molecules were highly expressed in the high-risk group. The 8-lactate metabolism gene-based prognostic model predicts patient survival, immune infiltration, and ICB response in patients with LUAD, driving the development of therapeutic strategies to target lactate metabolism.
    Journal • Checkpoint inhibition • Tumor mutational burden • Gene Signature • Checkpoint block
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
    |
    TMB-H
    22d
    Ensemble transformer-based multiple instance learning to predict pathological subtypes and tumor mutational burden from histopathological whole slide images of endometrial and colorectal cancer. (PubMed, Med Image Anal)
    Fisher's exact test further validated that the associations between the predictions of the proposed models and the actual cancer subtype or TMB status are both extremely strong (p<0.001). These promising findings show the potential of our proposed methods to guide personalized treatment decisions by accurately predicting the EC and CRC subtype and the TMB status for effective immunotherapy planning for EC and CRC patients.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H
    22d
    Extramammary Paget's disease treated with of anti-programmed cell death protein 1 therapy after docetaxel therapy failure. (PubMed, J Dermatol)
    Pembrolizumab is approved for solid tumors with a high tumor mutation burden (TMB) and/or high microsatellite instability, and nivolumab was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies. Even in the cases with a high TMB, the response to anti-PD-1 therapy was not sufficient. Most cases involve second-line or later treatments, so further research is needed to determine the precise effectiveness of anti-PD-1 therapy as a first-line treatment.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • docetaxel
    22d
    Whole Exome Sequencing of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Targets. (PubMed, Cancers (Basel))
    USP8 and NOTCH2 may serve as clinically relevant target for IECs. Finally, we present evidence that the crosstalk between the PI3K-Akt-mTOR and ECM signaling pathways may play a role in modulating the immune escape mechanism in IECs.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • NOTCH2 (Notch 2)
    |
    TMB-H
    24d
    Pembrolizumab efficacy in a tumor mutation burden-high glioblastoma patient: A case study and implications for precision oncology. (PubMed, Cancer Sci)
    A glioblastoma (GBM) patient with a high tumor mutation burden (TMB-high) and mismatch repair deficiency (dMMR) exhibited a significant response to pembrolizumab, an immune checkpoint inhibitor (ICI), despite prior treatment with temozolomide (TMZ), known to induce hypermutation and potential resistance to ICIs. The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This case challenges traditional GBM treatment paradigms, demonstrating the potential of precision oncology in patients with significant TMB and dMMR, and underscores the importance of comprehensive genomic profiling in guiding clinical decisions in GBM management.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • MSI-H/dMMR
    |
    Keytruda (pembrolizumab) • temozolomide
    25d
    Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database. (PubMed, JCO Precis Oncol)
    This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.
    Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • Stroma • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • NTRK (Neurotrophic receptor tyrosine kinase) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
    |
    TMB-H • NTRK3 fusion • HRD • ETV6-NTRK3 fusion • PDGFRA mutation • PDGFR wild-type
    |
    Keytruda (pembrolizumab)
    25d
    Multistage carcinogenesis in occupational cholangiocarcinoma: the impact of clonal expansion and risk estimation. (PubMed, Genes Environ)
    Three-stage ICC carcinogenesis has been proposed. The high mutation burden levels caused by occupational exposure led to an immediate incidence of cancer. After a long period of relatively low cancer risk, an increased risk in older adults was also predicted.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    25d
    SASS6 promotes tumor proliferation and is associated with TP53 and immune infiltration in lung adenocarcinoma. (PubMed, Clin Exp Med)
    In addition, patients with high SASS6 expression had worse immune infiltration, but higher TMB and immune checkpoint, and higher sensitivity to multiple targeted drugs such as osimertinib. Cell experiments confirmed that knockdown of SASS6 could inhibit the viability of tumor cells.SASS6 has important value in the diagnosis of cancer. In particular, SASS6 is a crucial factor in the progression of LUAD, and has important clinical value, especially in the diagnosis, prognosis and treatment.
    Journal
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Tagrisso (osimertinib)
    26d
    Identification and Validation of a Prognostic Signature Based on Fibroblast Immune-related Genes to Predict the Prognosis and Therapeutic Response of renal clear cell carcinoma by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data. (PubMed, J Cancer)
    This risk score and nomogram are valuable tools assessing KIRC patients' prognosis. Poorer prognosis in high-risk categories may have relationship with activation of coagulation pathway and a higher TMB.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    26d
    Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer (clinicaltrials.gov)
    P1, N=160, Terminated, Inhibrx Biosciences, Inc | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2025 --> Oct 2024; Program terminated due to lack of meaningful efficacy signal.
    Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Keytruda (pembrolizumab) • enristomig (INBRX-105)
    27d
    Immunotherapy in the treatment of rectal invasion by prostate cancer with focal neuroendocrine differentiation: a case report and literature review. (PubMed, Transl Androl Urol)
    TPE combined with immunotherapy may improve the prognosis. It is of utmost importance to achieve an accurate differential diagnosis, which necessitates the collaboration of multiple disciplines and the performance of requisite tests, including immunohistochemistry and genetic testing.
    Review • Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR
    28d
    Unlocking the Potential of Disulfidptosis-Related LncRNAs in Lung Adenocarcinoma: A Promising Prognostic LncRNA Model for Survival and Immunotherapy Prediction. (PubMed, Cancer Med)
    We developed a disulfidptosis-related risk model with 5 lncRNAs that enables survival prediciton for LUAD patients and aids cilinical decisions by forecasting the TME, TMB, and drug sensitivity, making it a valuable tool for outcomes prediction.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • SLC7A11 (Solute Carrier Family 7 Member 11)
    |
    TMB-H • SLC7A11 expression
    28d
    Establishing a predictive model for tumor mutation burden status based on 18F-FDG PET/CT and clinical features of non-small cell lung cancer patients. (PubMed, Transl Lung Cancer Res)
    In this study, a predictive model combining 18F-FDG PET/CT and clinical features of NSCLC patients effectively distinguished between TMB-high and TMB-low status. The nomogram generated from this model holds significant promise for predicting TMB status, offering valuable insights for clinical decision-making.
    Journal • Tumor mutational burden • IO biomarker • Predictive model • FDG PET
    |
    TMB (Tumor Mutational Burden) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    TMB-H • TMB-L
    28d
    Whole genome sequencing elucidates etiological differences in MCPyV-negative Merkel cell carcinoma. (PubMed, Pathol Res Pract)
    A rearrangement in the tumor suppressor gene SUFU was identified, a likely driver and potential target of the Hedgehog signaling pathway. Meanwhile, the second case exhibited a less aggressive behavior, harbored UV-signature mutations, and a high mutational burden including mutations in TP53 and RB1.
    Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • SUFU (SUFU Negative Regulator Of Hedgehog Signaling)
    |
    TP53 mutation • TMB-H • TMB-L
    29d
    Non-B DNA-informed mutation burden as a marker of treatment response and outcome in cancer. (PubMed, Br J Cancer)
    These novel markers offer a nuanced approach to enhance our understanding of treatment responses and outcomes in cancer, underscoring the need for a comprehensive exploration of the interplay between non-B and B-DNA features.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    cisplatin
    30d
    Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia. (PubMed, Lung Cancer)
    Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.
    Journal • Checkpoint inhibition • Tumor mutational burden • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
    |
    EGFR mutation • TMB-H • HER-2 mutation • HER-2 exon 20 insertion • ALK fusion • HER-2 exon 20 mutation
    1m
    MRI-based radiomics model for predicting endometrial cancer with high tumor mutation burden. (PubMed, Abdom Radiol (NY))
    The MRI-based radiomics models demonstrated moderate predictive ability for TMB-H EC and thus may be a tool for preoperative, noninvasive prediction of TMB-H EC.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    1m
    Role of disulfidptosis in colorectal adenocarcinoma: implications for prognosis and immunity. (PubMed, Front Immunol)
    We also predicted that drugs such as 5-Fluorouracil, Oxaliplatin, Gefitinib, and Sorafenib would be more effective in low-risk patients, while drugs like Luminesib and Staurosporine would be more effective in high-risk patients. Finally, the expression of these key genes was verified in clinical samples, with consistent results. Our research findings provide evidence for the role of disulfidptosis in COAD and offer new insights for personalized and precise treatment of COAD.
    Journal • MSi-H Biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CCL11 (C-C Motif Chemokine Ligand 11) • SLC7A11 (Solute Carrier Family 7 Member 11) • HOXC6 (Homeobox C6)
    |
    TMB-H • MSI-H/dMMR • SLC7A11 expression
    |
    gefitinib • sorafenib • 5-fluorouracil • oxaliplatin
    1m
    Glomus Tumor of the Chest Wall With Metastases to Lung. (PubMed, Cureus)
    We present a 67-year-old female diagnosed with a chest wall glomus tumor with biopsy-proven metastases to her lungs. Her treatment course included neoadjuvant radiation therapy followed by immunotherapy with pembrolizumab...This case provided encouraging results for treatment with radiation and, potentially, immunotherapy. Each instance of a malignant glomus tumor and its genetic profile should be closely examined and documented so that sufficient data can be accumulated to guide treatment for this rare cancer.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Keytruda (pembrolizumab)