^
    1d
    ASTEROID: A Trial of ASTX660 in Combination With Pembrolizumab (clinicaltrials.gov)
    P1, N=61, Active, not recruiting, Institute of Cancer Research, United Kingdom | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026
    Enrollment closed • Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TERT (Telomerase Reverse Transcriptase)
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    HER-2 positive • ER positive • HER-2 negative • EGFR amplification • IDH wild-type • ER positive + HER-2 negative • HER-2 negative + ER positive
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    Keytruda (pembrolizumab) • tolinapant (ASTX660)
    1d
    A Phase II Study to Evaluate the Efficacy and Safety of SKB571 in Recurrent or Metastatic HNSCC Participants (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
    New P2 trial
    1d
    APG-157 in Locally Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P3, N=826, Not yet recruiting, Aveta Biomics, Inc.
    New P3 trial
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    cisplatin • carboplatin
    1d
    Genomic Landscape of Oral Squamous Cell Carcinoma in Never Smokers and Never Drinkers. (PubMed, Asian Pac J Cancer Prev)
    Together, these data suggest that mucin genes, specifically MUC16 and MUC5B, are important for oral carcinogenesis in the absence of tobacco and alcohol. These results are relevant given the increasing clinical utility of mucins as druggable targets in cancer, particularly MUC16.
    Journal
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    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • MUC16 (Mucin 16, Cell Surface Associated) • CASP8 (Caspase 8) • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming)
    1d
    Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers. (PubMed, J Exp Clin Cancer Res)
    Our findings define a tumor-stroma metabolic cooperation axis in which TGFβ2-driven lipid exchange sustains adaptive cetuximab tolerance in HNSCC. Targeting TGFβ2-mediated stromal reprogramming or FA transfer represents a promising strategy to delay or overcome resistance to EGFR-targeted therapies.
    Journal
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    TGFB2 (Transforming Growth Factor Beta 2)
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    Erbitux (cetuximab)
    1d
    The inflammatory microenvironment in patients with advanced and relapsing hypopharyngeal squamous cell carcinoma. (PubMed, Am J Otolaryngol)
    These findings indicate that HPSCC is a highly immunogenic tumour entity. Components of the TME, particularly FX_CD68-positive TAMs, may represent promising biomarkers for risk stratification and could support the development of personalised therapeutic strategies.
    Journal
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    CD68 (CD68 Molecule)
    1d
    Nutritional Amino Acid Supplementation Reduces Severity and Enhances Recovery of Radiation-Induced Oral Mucositis: A Triple-Blind Randomized Clinical Trial. (PubMed, J Oral Rehabil)
    Oral arginine and glutamine supplementation was associated with reduced severity and enhanced recovery of RIOM. Nutritional amino acid supplementation may represent a useful adjunct in supportive oral care and oral rehabilitation for patients undergoing radiotherapy.
    Clinical • Journal
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    IL6 (Interleukin 6) • EGF (Epidermal growth factor)
    1d
    A Phase 2 Feasibility Study Combining Pembrolizumab and Metformin in patients with Metastatic Head and Neck Cancer. (PubMed, Clin Cancer Res)
    The combination of metformin and pembrolizumab was well tolerated with mild GI-associated AEs and promising activity warranting further investigation in a randomized trial.
    P2 data • Journal
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    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1)
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    Keytruda (pembrolizumab) • metformin
    1d
    Tumoral and Systemic Immune Correlates of Response to Concurrent Pembrolizumab and Chemoradiotherapy in Patients with Resected High-Risk Head and Neck Squamous Cell Carcinoma. (PubMed, Clin Cancer Res)
    These findings highlight multiple potential immunologic correlates of pembrolizumab with CRT in high-risk HNSCC, supporting further evaluation and validation in larger, adequately powered trials.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2) • ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1) • GZMK (Granzyme K) • NECTIN2 (Nectin Cell Adhesion Molecule 2)
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    PD-L1 expression • TP53 mutation
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    Keytruda (pembrolizumab) • cisplatin
    1d
    Targeting the KMT2D-driven Enhancer-Immune-Metabolic axis in HNSCC: Reconciling the paradox for precision therapy. (PubMed, Biochim Biophys Acta Rev Cancer)
    KMT2D-driven enhancer remodeling provides a unifying lens to connect metabolic reprogramming with immune escape in HNSCC. Conceptualizing KMT2D as an epigenetic rheostat supports biomarker-informed combination strategies-integrating DNA damage repair targeting, metabolic interventions, and epigenetic priming-to overcome ICB resistance and improve durable disease control in KMT2D-altered HNSCC.
    Review • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KMT2D (Lysine Methyltransferase 2D) • PER2 (Period Circadian Regulator 2)
    1d
    Perturbation of the circadian rhythmic transcription contributes to radiotherapy-induced salivary gland hypofunction. (PubMed, Commun Biol)
    Modulation of the circadian clock by chemical agents including Nobiletin and SR1078 can reduce the damaging effect and improve saliva production. We propose that the salivary gland hypofunction after radiotherapy involves perturbation of the circadian rhythmic transcription, which can be partially rescued by chemical agents that improve the circadian rhythm.
    Journal
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    ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like) • NR1D1 (Nuclear Receptor Subfamily 1 Group D Member 1)
    1d
    Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer (clinicaltrials.gov)
    P1/2, N=120, Not yet recruiting, National Cancer Institute (NCI)
    New P1/2 trial
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    docetaxel • SX-682