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    GENE:

    SMAD4 (SMAD family member 4)

    i
    Other names: HSMAD4, Mothers Against DPP Homolog 4, SMAD, Mothers Against DPP Homolog 4, Deleted In Pancreatic Carcinoma Locus 4, SMAD, Mothers Against DPP Homolog 4, Mothers Against Decapentaplegic, Drosophila, Homolog Of, 4, MADH4, MAD, Mothers Against Decapentaplegic Homolog 4, Mothers Against Decapentaplegic Homolog 4, MAD Homolog 4, SMAD4, SMAD Family Member 4, Deletion Target In Pancreatic Carcinoma 4
    3d
    Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing. (PubMed, Histol Histopathol)
    Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.
    Journal • Next-generation sequencing • IO Complimentary diagnostic
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4)
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    TP53 mutation • KRAS mutation
    4d
    Uncovering molecular pathways in appendiceal cancer: A comprehensive characterization for precision oncology. (PubMed, Am J Surg)
    This study offers a comprehensive molecular characterization of AC, comparing distinct oncogenic pathway signatures between primary and metastatic disease. The identification of pathway-specific alterations offers valuable insights into the molecular heterogeneity of AC and highlights opportunities for pathway-targeted therapies. These findings emphasize the importance of integrative molecular profiling to advance precision oncology and improve outcomes for patients with this rare malignancy.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1)
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    TP53 mutation
    7d
    STAT3-mediated transactivation of NOVA2 promotes lung adenocarcinoma metastasis by splicing SMAD4. (PubMed, Oncogene)
    Moreover, in NOVA2-overexpressing LUAD cells, Δ-SMAD4 knockdown has stronger inhibitory effects on TGF-β-induced EMT and invasion than does SMAD4 knockdown. In summary, our findings identify a novel mechanism by which STAT3-mediated transcriptional upregulation of NOVA2 promotes SMAD4 splicing in metastatic LUAD, and suggest that the STAT3-NOVA2-Δ-SMAD4 axis drives EMT and LUAD metastasis, which may be a promising therapeutic target for treating LUAD.
    Journal
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    SMAD4 (SMAD family member 4) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TGFB1 (Transforming Growth Factor Beta 1) • SMAD3 (SMAD Family Member 3)
    8d
    Neoadjuvant Chemotherapy Diminishes Ki-67 Overexpression and Persistent Overexpression is a Poor Prognostic Factor in Pancreatic Ductal Adenocarcinoma After Pancreatectomy. (PubMed, Pancreas)
    NAC diminishes Ki-67 overexpression, and persistent overexpression even after NAC is an independent poor prognostic factor of PDAC after pancreatectomy. The Ki-67 overexpression may mirror a high malignant state due to the low SMAD4 and high c-Myc expression.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SMAD4 (SMAD family member 4)
    8d
    FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression. (PubMed, Cell Death Dis)
    In this study, we identified defactinib, a specific inhibitor of FAK as a novel ferroptosis suppressors...Notably, elevated FAK/SRC-JNK signaling sensitizes cancer cells to ferroptosis-inducing therapies, while inhibition of the FAK/SRC-JNK signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings highlight the central role of FAK/ SRC-JNK signaling in controlling ferroptotic cell death and underscore the therapeutic potential of targeting FAK/ SRC-JNK mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.
    Journal
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    SMAD4 (SMAD family member 4) • STAT3 (Signal Transducer And Activator Of Transcription 3) • ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • ATF2 (Activating Transcription Factor 2) • HSF1 (Heat Shock Transcription Factor 1) • NFATC3 (Nuclear Factor Of Activated T Cells 3)
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    Fakzynja (defactinib)
    10d
    LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)
    P=N/A, N=5909, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting
    Enrollment open
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • RAD51D (RAD51 paralog D) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • DICER1 (Dicer 1 Ribonuclease III) • FLCN (Folliculin) • PRSS1 (Serine Protease 1) • SDHD (Succinate Dehydrogenase Complex Subunit D) • TXNIP (Thioredoxin Interacting Protein) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • HOXB13 (Homeobox B13)
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    TP53 mutation • PTEN deletion
    11d
    Cytomorphologic and molecular characterization of metastatic renal cell carcinoma diagnosed by fine-needle biopsy: a single-institution study. (PubMed, J Am Soc Cytopathol)
    FNB is frequently used as the primary diagnostic modality for mRCC and can provide sufficient material for histologic classification and, in selected cases, molecular profiling. Integration of cytology and genomic data from FNB specimens may aid diagnostic classification in selected cases, particularly when morphology and immunohistochemistry are limited.
    Journal
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • SMAD4 (SMAD family member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • FAT3 (FAT Atypical Cadherin 3)
    12d
    Polyploid and Chromosomal Copy Number Gain Cells in Metastatic Colon Cancer: Exploratory Genotype-Phenotype Correlations. (PubMed, Cancers (Basel))
    In metastatic colon cancer, the presence of genome-wide copy number gain may delineate a tumor subset with distinctive clinicopathological and molecular characteristics. Further studies are warranted to elucidate the biological significance of these features and to explore their potential implications for tumor evolution, treatment response, and clinical stratification.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • SMAD4 (SMAD family member 4)
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    TP53 mutation • BRAF mutation • HER-2 amplification • RAS mutation
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    TruSight Oncology 500 Assay
    12d
    Anticancer effects of salidroside on ovarian cancer carcinogenesis and molecular mechanism in mice. (PubMed, Biomed Pharmacother)
    It can suppress the carcinogenesis, progression, and growth of ovarian cancer by upregulating the expression of PTEN, ARID1A, TGF-β, and SMAD4, increasing the production of CA125, VEGF-A, IL-2, and IL-10, and elevating the levels of CD3+, CD8+, and Treg cells in the ascites. SAL at a dose of 400 μg/g exhibited the most potent inhibitory effect on ovarian cancer, which lays a solid foundation for the development of salidroside as a novel anticancer drug.
    Preclinical • Journal
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    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • SMAD4 (SMAD family member 4) • MUC16 (Mucin 16, Cell Surface Associated) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • TGFB1 (Transforming Growth Factor Beta 1)
    12d
    Biomarkers in Colorectal Cancer: Clinically Relevant Diagnostic and Prognostic Molecular Features, and the Future of Precision Medicine. (PubMed, J Pers Med)
    This review explores the mutations and co-mutations most relevant to CRC, their prevalence, prognostic significance, and implications for precision oncology. By focusing on these genetic and epigenetic alterations, we aim to contextualize how biomarker-driven strategies are reshaping the management of CRC in both early and advanced disease settings.
    Review • Journal • MSi-H Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4)
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    TP53 mutation • KRAS mutation • MSI-H/dMMR • PIK3CA mutation
    13d
    SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer. (PubMed, Adv Sci (Weinh))
    Notably, clinically relevant SMAD4 mutants (R361C and R361H) exhibit enhanced palmitoylation, underscoring the pathological relevance of this mechanism for tumorigenesis. Collectively, these findings unveil a metabolic-transcriptional circuit wherein palmitoylation bridges lipid metabolism with SMAD4-driven oncogenesis, and posit SMAD4 palmitoylation as a therapeutic vulnerability in pancreatic cancer.
    Journal
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    SMAD4 (SMAD family member 4) • FASN (Fatty acid synthase) • ZDHHC22 (Zinc Finger DHHC-Type Palmitoyltransferase 22)
    15d
    A retrospective analysis of taxane-based chemotherapy in small bowel adenocarcinoma. (PubMed, Oncologist)
    Taxane-based therapy demonstrated activity in metastatic SBA, with 24% response and 3.1-month mTTP. TP53 mutation may be a negative predictive marker for taxane efficacy. These findings support prospective investigation in metastatic SBA.
    Retrospective data • Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • SMAD4 (SMAD family member 4)
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    TP53 mutation • KRAS mutation