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The William Harvey Research Institute - Faculty of Medicine and Dentistry

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  5. BC-DTP_2026_06

Head and Neck Cancer-Specific Mechanisms of Neural Invasion

Code: BC-DTP_2026_06

Title: Head and Neck Cancer-Specific Mechanisms of Neural Invasion

Primary Supervisor: Ana Caetano 

Email: a.caetano@qmul.ac.uk  

Institute: Institute of Dentistry 

Secondary Supervisor: Krishna Suchak 

Email: krishna.suchak@nhs.net

Institute: Barts Health NHS Pathology (Consultant Pathologist) 

Lay Summary:

Cancer spreading along nerves, called perineural invasion, is common in head and neck cancers and strongly predicts tumors returning after treatment, severe pain, and spread to other organs. Yet we don't understand how cancers recruit nerves or why some tumors invade nerves more aggressively than others. We discovered that glial cells - the supporting cells that normally protect nerves, change their identity in tumors. These tumor-associated glia express neuronal features and reactivate developmental programs, shifting from their mature protective state to an immature nerve-building state. We hypothesize that this neurogenic shift actively promotes tumor innervation, driving the poor outcomes linked to nerve-dense cancers. Supporting this, tumors with high neural invasion express distinct patterns of glial markers compared to less invasive cancers. This project will determine how cancer microenvironments reprogram glial cells and whether this reprogramming enables nerve recruitment. We will map glial cell states using genomic and epigenomic profiling, test whether neurogenically reactivated glia functionally support tumor innervation through mouse models and cellular experiments, and identify the molecular signals that activate or suppress this glial plasticity. This research directly addresses oral cancer disparities in East London's South Asian and Bangladeshi communities, who face higher cancer rates and later diagnoses leading to worse outcomes. Understanding nervous system responses to cancer could reveal early biomarkers distinguishing aggressive from less aggressive disease and identify therapeutic targets that block cancer from spreading along nerves - directly benefiting communities experiencing the greatest oral cancer burden.

Aims:

Aim 1: To define innervation landscapes and neuroglia molecular phenotypes in highly neurotropic lesions (ACC) versus less neuroinvasive lesions (MEC, OSCC).

Aim 1.1: Characterise innervation density and spatial organisation across cancer types.

Aim 1.2: Map glial transcriptional and epigenomic states in neurotropic versus non-neurotropic tumors.

Aim 2: To identify mechanisms controlling glia neurogenic plasticity.

Aim 2.1: To identify and validate regulators of glia neurogenic competence.

Aim 2.2: To test whether manipulating glia prevents tumour innervation in vivo.

References:

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  6. Mody MD, Rocco JW, Yom SS, Haddad RI, Saba NF. Head and neck cancer. Lancet. 2021;398(10318):2289–99.
  7. Parikh AS, Wizel A, Davis D, Lefranc-Torres A, Rodarte-Rascon AI, Miller LE, et al. Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma. Cell Rep. 2022;41(9):111743.
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