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    BIOMARKER:

    TMB-H

    i
    Other names: TMB | Tumor Mutational Burden
    Related biomarkers:
    Expression
    Others
    Related tests:
    13h
    If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide. (PubMed, Med)
    They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.
    Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • CD70 (CD70 Molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • TMB-H • BRAF V600 • HER-2 expression • RET fusion • FGFR mutation • FGFR fusion • PD-L1 amplification • FGFR1 expression • IDH mutation + BRAF V600E • IDH mutation + NTRK fusion • NTRK fusion
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Retevmo (selpercatinib) • Jemperli (dostarlimab-gxly) • Pemazyre (pemigatinib) • Augtyro (repotrectinib)
    16h
    A Study of BGB-30813 Alone or in Combination With Tislelizumab in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=200, Recruiting, BeiGene | Active, not recruiting --> Recruiting | N=37 --> 200 | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026
    Enrollment open • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR
    |
    Tevimbra (tislelizumab-jsgr) • BGB-30813
    1d
    Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature. (PubMed, Cancers (Basel))
    This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.
    Journal • Real-world evidence • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L • DDR signature score
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    1d
    High Prevalence of TBC1D12 5'UTR Mutations in Anaplastic Thyroid Cancer. (PubMed, Thyroid)
    TBC1D12 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, p = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, p = 0.010), and advanced tumor stages (85.7% vs. 32.5%, p = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of TBC1D12 5'UTR mutations in ATC and indicated an association between TBC1D12 mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • TERT (Telomerase Reverse Transcriptase) • ADGRG6 (Adhesion G Protein-Coupled Receptor G6) • SDHD (Succinate Dehydrogenase Complex Subunit D)
    |
    BRAF V600E • TMB-H • BRAF V600 • TERT mutation • TERT promoter mutation
    2d
    The genomic landscape of cutaneous squamous cell carcinoma in Japan. (PubMed)
    TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.
    Journal • Tumor mutational burden
    |
    FoundationOne® CDx
    2d
    Addition of SHR-1701 to first-line capecitabine and oxaliplatin (XELOX) plus bevacizumab for unresectable metastatic colorectal cancer. (PubMed, Signal Transduct Target Ther)
    Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    TMB-H
    |
    capecitabine • oxaliplatin • retlirafusp alfa (SHR-1701) • Airuituo (bevacizumab biosimilar)
    2d
    Tumor mutational burden as a marker for radiologic response to immune checkpoint inhibitors. (PubMed, Curr Probl Diagn Radiol)
    Higher TMB was associated with objective response to ICI, however, TMB was an imperfect biomarker for PFS and OS in our study.
    Journal • Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab)
    3d
    Squamous cell carcinoma arising in chronically damaged skin (Marjolin's Ulcer): still an unmet need in the era of immunotherapy. (PubMed, Oncologist)
    This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Keytruda (pembrolizumab) • Libtayo (cemiplimab-rwlc) • anti-PD-1 antibody
    4d
    The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study. (PubMed, Lancet Oncol)
    Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy.
    Observational data • Retrospective data • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    doxorubicin hydrochloride • cyclophosphamide • etoposide IV • vincristine • dacarbazine • Leukeran (chlorambucil) • Matulane (procarbazine hydrochloride) • bleomycin • vinblastine
    4d
    Enhancing the detection of clinically relevant biomarkers in advanced uterine and tubo-ovarian carcinomas through genome-wide analysis. (PubMed, Pathol Res Pract)
    Comprehensive genomic profiling of advanced-stage TOC and UC via WGS reveals key biomarkers and therapeutic targets, enhancing diagnostic accuracy and advancing personalized medicine in gynecological cancers.
    Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)
    |
    TMB-H • HRD • BRCA wild-type • CCNE1 amplification
    5d
    Negative response to immunotherapy in dMMR or MSI-H gastric cancer with APC and PTEN mutations: a case report. (PubMed, Front Oncol)
    We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients. Mutations of key genes within tumor-related signaling pathways and the infiltration of CD8+T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CD8 (cluster of differentiation 8) • APC (APC Regulator Of WNT Signaling Pathway)
    |
    PD-L1 expression • TMB-H • MSI-H/dMMR • PD-L1 overexpression • PTEN deletion • PTEN mutation • APC mutation
    6d
    Bioinformatics insights into the role of GFPT1 in breast invasive carcinoma: implications for tumor prognosis, immune modulation, and therapeutic applications. (PubMed, Front Genet)
    These findings indicate that GFPT1 is a novel prognostic biomarker and a predictive indicator of chemotherapy response in invasive breast carcinoma. GFPT1 influences mRNA translation, cell cycle regulation, and M2 macrophage infiltration, thereby promoting cancer cell proliferation and metastasis.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • TMB-H • BRCA mutation
    7d
    Melanoma Tumor Mutational Burden and Indoor Tanning Exposure. (PubMed, JAMA Dermatol)
    This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    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)
    8d
    Complete remission after pembrolizumab monotherapy in a non-small cell lung cancer patient with PD-L1 negative, high tumor mutational burden, and positive tumor-infiltrating lymphocytes: A case report. (PubMed, Medicine (Baltimore))
    A comprehensive evaluation of multiple tumor biomarkers should be considered in NSCLC patients. Pembrolizumab monotherapy could benefit NSCLC patients with negative driver genes, PD-L1 negative, a high tumor mutational burden, and positive tumor-infiltrating lymphocytes.
    Journal • Tumor mutational burden • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
    |
    TMB-H • PD-L1 negative
    |
    Keytruda (pembrolizumab)
    12d
    High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients. (PubMed, J Transl Med)
    Our results highlight the prognostic significance of TMB in MSS metastatic colon cancer patients, suggesting its potential role in patient stratification and treatment decision-making.
    Journal • Next-generation sequencing • Tumor mutational burden • MSi-H Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • TMB-L • RAS mutation
    13d
    TMB is associated with the prognosis of egfr-mutated non-small cell lung cancer in Xuanwei, China. (PubMed, Biomark Med)
    Further analysis of accompanying mutations and TMB levels revealed an association between high TMB and a favorable prognosis in EGFR-mutated Xuanwei NSCLC. Xuanwei lung cancer differs from non Xuanwei patients in terms of prognosis and tumor mutation burden, and further research should be conducted.
    Journal • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden)
    |
    EGFR mutation • TMB-H
    14d
    A 5-year review of genomic medicine in breast cancer: insights from C-CAT data on 3776 Japanese patients. (PubMed, Breast Cancer)
    These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.
    Review • Journal • MSi-H Biomarker • MSi-H Companion diagnostic
    |
    BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • ER positive • TMB-H • MSI-H/dMMR • HER-2 negative • BRAF V600 • HER-2 negative + ER positive • NTRK fusion
    |
    fulvestrant • Truqap (capivasertib)
    15d
    Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma (clinicaltrials.gov)
    P1, N=110, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Keytruda (pembrolizumab)
    16d
    Blood-based tumor mutational burden impacts clinical outcomes of immune checkpoint inhibitor treated breast and prostate cancers. (PubMed, Commun Med (Lond))
    In this study, the practice of offering an ICIs based on bTMB was uncommon and did not independently predict ICI benefits in patients with refractory, advanced breast and prostate cancers.
    Clinical data • Journal • Checkpoint inhibition • Tumor mutational burden • BRCA Biomarker • IO biomarker
    |
    ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1)
    |
    TMB-H • TMB-L
    17d
    Investigation and validation of neurotransmitter receptor-related biomarkers for forecasting clinical outcomes and immunotherapeutic efficacy in breast cancer. (PubMed, Gene)
    Risk prediction model based on DLG3, SLC1A1, PSCA and PRKCZ, which are closely related to BC prognosis, was successfully constructed.
    Clinical data • Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • PSCA (Prostate Stem Cell Antigen 2) • DLG3 (Discs Large MAGUK Scaffold Protein 3)
    |
    TMB-H
    18d
    Deciphering potential molecular mechanisms in clear cell renal cell carcinoma based on the ubiquitin-conjugating enzyme E2 related genes: Identifying UBE2C correlates to infiltration of regulatory T cells. (PubMed, Biofactors)
    This study presents a novel three-gene prognostic model based on UBE2RGs that demonstrates significant predictive value for OS, immunotherapy, and chemotherapy in ccRCC patients. The findings underscore the potential of UBE2 family members as biomarkers and therapeutic targets in ccRCC, warranting further investigation in prospective clinical trials.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • TGFB1 (Transforming Growth Factor Beta 1) • UBE2C (Ubiquitin Conjugating Enzyme E2 C) • UBE2D3 (Ubiquitin Conjugating Enzyme E2 D3)
    |
    TMB-H
    19d
    A Case of Advanced Extramammary Paget's Disease With a High Tumor Mutation Burden That Showed Partial Lymph Node Regression With Pembrolizumab. (PubMed, Cureus)
    We started a combination chemotherapy of tegafur-gimeracil-oteracil potassium (TS-1) and docetaxel. After four cycles of the pembrolizumab treatment, a CT scan showed further shrinkage in most of the lymph node metastases. As far as we know, the present patient is the first case of advanced EMPD with response to pembrolizumab monotherapy.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    |
    Keytruda (pembrolizumab) • docetaxel • Teysuno (gimeracil/oteracil/tegafur)
    19d
    Myxofibrosarcoma with epithelioid morphology: A clinicopathological study of 44 cases with emphasis on differential diagnosis. (PubMed, Histopathology)
    These findings suggest that UV-driven malignancies (including melanoma or sarcomatoid squamous cell carcinoma) may histologically mimic eMFS and should be considered in cases of eMFS presenting at atypical anatomical sites.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    TMB-H • NRAS mutation • NRAS Q61
    20d
    A novel disulfidptosis-related LncRNA prognostic risk model: predicts the prognosis, tumor microenvironment and drug sensitivity in esophageal squamous cell carcinoma. (PubMed, BMC Gastroenterol)
    We established a DRG-lncRNA prognostic model that can be used to predict the prognosis, tumor mutation burden, immune cell infiltration, and drug sensitivity of ECSS patients. The results of this study provide valuable insights into the understanding of ESCC and provide valuable assistance for the individualized treatment of ESCC patients.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L
    21d
    The MHC-I-dependent neoantigen presentation pathway predicts response rate to PD-1/PD-L1 blockade. (PubMed, Biomol Biomed)
    Importantly, combining antigen expression, processing, presentation, and recognition features provides superior predictive power compared to TMB alone. This integrated approach could improve treatment outcome predictions and advance personalized immunotherapy strategies.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • HLA-A (Major Histocompatibility Complex, Class I, A)
    |
    TMB-H • CD8 expression
    21d
    Genomic Analysis of Advanced Phyllodes Tumors Using Next-Generation Sequencing and Their Chemotherapy Response: A Retrospective Study Using the C-CAT Database. (PubMed, Medicina (Kaunas))
    One patient with a high tumor mutational burden (37/Mb) responded to pembrolizumab... Our findings suggest distinct molecular patterns in phyllodes tumors compared to other soft tissue sarcomas, with potential implications for treatment selection. The identification of specific genetic alterations associated with treatment resistance may guide therapeutic decision-making, while the presence of actionable mutations in select cases indicates potential opportunities for targeted therapy approaches.
    Retrospective data • Journal • Next-generation sequencing • Tumor mutational burden • PD(L)-1 Biomarker • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH6 (MutS homolog 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • TMB-H
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    |
    Keytruda (pembrolizumab)
    21d
    Association of Genomic Alterations with the Presence of Serum Monoclonal Proteins in Chronic Lymphocytic Leukemia. (PubMed, Cells)
    An IgM monoclonal protein was associated with TP53 mutations (36% in IgM +sIFE vs. 12% in non-IgM +sIFE or -sIFE, p = 0.04), and bi/triclonal proteins with NOTCH1 mutations (33% in bi/triclonal vs. 9% in monoclonal +sIFE or -sIFE, p = 0.04). These data suggest an association between a +sIFE and a higher mutational burden, and some monoclonal isotypes with specific mutations.
    Retrospective data • Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NOTCH1 (Notch 1) • IGH (Immunoglobulin Heavy Locus)
    |
    TP53 mutation • TMB-H • NOTCH1 mutation
    23d
    Cancers adapt to their mutational load by buffering protein misfolding stress. (PubMed, Elife)
    We replicate these expression responses in cancer cell lines and show that the viability in high mutational load cancer cells is strongly dependent on complexes that degrade and refold proteins. This indicates that the upregulation of proteostasis machinery is causally important for high mutational burden tumors and uncovers new therapeutic vulnerabilities.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H
    25d
    Integration of the bulk transcriptome and single-cell transcriptome reveals efferocytosis features in lung adenocarcinoma prognosis and immunotherapy by combining deep learning. (PubMed, Cancer Cell Int)
    Our study developed a novel prognostic signature of efferocytosis-related genes. This prognostic signature accurately predicted survival prognosis as well as treatment outcome in LUAD patients and explored the role of HAVCR1 in lung adenocarcinoma progression.
    Journal • IO biomarker
    |
    TMB (Tumor Mutational Burden) • KIM1 (Kidney injury molecule 1)
    |
    TMB-H
    26d
    Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma. (PubMed, Ann Surg Oncol)
    Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    TMB-H • PALB2 mutation
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    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
    28d
    Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors. (PubMed, JCO Precis Oncol)
    This study demonstrates that NGS-MSI is noninferior to IHC-MMR and can identify MSI-H tumors that IHC-MMR is unable to detect and conversely IHC-MMR can identify MMRd tumors that NGS-MSI misses.
    Journal • Next-generation sequencing • Mismatch repair • Tumor mutational burden • Microsatellite instability • MSi-H Biomarker • IO biomarker • Discordant
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TMB-H • MSI-H/dMMR
    29d
    Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer. (PubMed, Biol Direct)
    The 20-gene model offers a cost-efficient approach to precisely estimating TMB, providing prognosis in patients with CRC. Incorporating DNAH5 within this model further refines the categorization of patients with elevated TMB. Utilizing the 20-gene model facilitates the stratification of patients with CRC, enabling more precise treatment planning.
    Journal • Tumor mutational burden • IO biomarker • Machine learning
    |
    TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
    |
    TMB-H
    29d
    Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1) (clinicaltrials.gov)
    P1/2, N=53, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed
    Trial completion
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    TMB-H • MSI-H/dMMR
    |
    bintrafusp alfa (M7824) • epacadostat (INCB024360) • Anktiva (nogapendekin alfa inbakicept-pmln)
    29d
    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
    1m
    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)
    1m
    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
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden)
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    TP53 mutation • KRAS mutation • TMB-H • TMB-L
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    TruSight Oncology 500 Assay
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    cisplatin • Imfinzi (durvalumab) • gemcitabine
    1m
    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
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    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)
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    KRAS mutation • TMB-H • MET overexpression • PTPRT mutation
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    GuardantINFINITY™
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    telisotuzumab adizutecan (ABBV-400) • telisotuzumab (h224G11)
    1m
    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
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    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)
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    TMB-H • MSI-H/dMMR
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    TruSight Oncology 500 Assay
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    oxaliplatin • irinotecan
    1m
    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
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    TMB (Tumor Mutational Burden)
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    TMB-H • TMB-L
    1m
    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
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8)
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    TMB-H • PD-L1 overexpression
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    Imfinzi (durvalumab) • Xtandi (enzalutamide) • Imjudo (tremelimumab) • abiraterone acetate