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NIH grant 1R01DE035884-01: Salivary Neural Development Programs Enable Adenoid Cystic Carcinoma Progression
Institute: {'code': 'DE', 'abbreviation': 'NIDCR', 'name': 'National Institute of Dental and Craniofacial Research', 'admin_org_id': '12500070', 'admin_funding_url': ''}. PI: Richard J Wong. Award: $769938.
Start: 2026-07-22T00:00:00.
PROJECT SUMMARY/ABSTRACT
Adenoid cystic carcinoma (ACC) is a rare, aggressive salivary gland malignancy characterized by frequent
recurrence, perineural invasion, and poor long-term survival. Despite advances in targeted and immune-based
therapies, clinical outcomes remain unsatisfactory, underscoring the need for novel therapeutic strategies. A
hallmark of ACC is its consistent association with nerves, but the biological significance of this phenomenon
remains poorly understood. Recent studies on other malignancies have shown that tumor innervation can
actively promote cancer progression. Transcriptomic analyses of ACC tumors revealed that elevated
noradrenergic gene expression signatures correlate with poor patient survival. Single-cell RNA sequencing and
Visium HD spatial transcriptomics further demonstrated the activation of β2-adrenergic signaling pathways in
ACC cells and spatial co-localization with sympathetic developmental gene signatures. These findings suggest
that sympathetic neural programs may play a critical role in ACC progression.
This proposal aims to characterize tumor innervation in ACC and evaluate its therapeutic potential. Aim 1 will
generate comprehensive neuronal maps of ACC tumors, correlating nerve type, density, morphology, and
maturity with clinical, pathological, and genomic features. Aim 2 will define the relationships between nerves
and ACC cells using neurotransmitter stimulation assays, spatial transcriptomics, and single-nucleus RNA
sequencing. Aim 3 will assess the therapeutic impact of targeting tumor innervation through nerve ablation
strategies in patient-derived xenograft models and investigate the role of MYB and Notch1 oncogenes in
mediating neural development in ACC.
Collectively, this work will elucidate the role of tumor innervation in ACC and may identify novel therapeutic
targets to improve outcomes for patients with this challenging disease.document fetched 2026-08-02 08:24