The main aim of the present project is to contribute to the improvement of diagnostic and prognostic routine methodologies for Head and Neck Squamous Cell Carcinoma (HNSCC).
The identification of predictive early biomarkers from blood-derived Circulating Tumour Cells (CTCs) combined with non-invasive methodology, like liquid biopsy is crucial for patients screening and represent a powerful platform for future personalized therapy to improve survival rate and decrease the incidence of recidivating tumours.
Unfortunately, no prognostic markers are currently available for HNSCC because of low number of CTCs and low sensitivity and false negative results arising from traditional approaches based on surface adhesion molecules, including EpCAM, citokeratin and beta-catenin.
To overcome these limitations, we propose the development and validation of TripleQuad/SelexION-based high-throughput and high-sensitivity mass spectrometry approaches to implement the analytical and regulatory detection of key determinants in blood derived CTCs from HNSCC.
Based on our previous works and current literature, we hypothesize that the receptors for the mature nerve growth factor (NGF) and its precursor form (proNGF), namely p75 neurotrophic receptor (p75NTR) and Tyrosine kinase A (TrkA), are involved in cancer cells survival, proliferation, and spreading, and represent a promising marker in squamous tumour, like HNSCC.
In line with this working hypothesis, our preliminary results showed increased level of p75NTR and of cancer-associated TrkA variant TrkAIII in tumour tissues from a small group of LSCC patients, as compared to the healthy controls.
Overall, based on the promising data hereby collected, and combining classical biochemical methods with the most advanced proteomic analysis, we envisage a significant correlation between NGF receptor variants with tumour aggressiveness, pinpointing their potential as specific and novel blood biomarkers for HNSCC personalized therapy.