Cutaneous Squamous Cell Carcinoma (cSCC) and its precursors, actinic keratosis and Bowen's disease, are the most common types of keratinocytic skin lesions (KSLs) which account for the majority of non-melanoma skin cancer lethality. Currently, clinical and histopathological criteria are used for the diagnosis, classification and therapeutic intervention of KSLs. However, discrepancies exist between the clinical presentations and histologic analyses of these lesions, making the diagnosis difficult. The identification of biomarkers as companion diagnostics for accurately stratifying KSL types is required to support the paradigm shift in current cancer care to personalized, precision medicine and ameliorate the negative impact of misdiagnoses or delayed diagnoses on patient outcome. Also, it is essential to elaborate on the poorly defined molecular modifications required for the initiation, development and progression of KSLs from normal keratinocytes. The development of non-invasive tools such as liquid biopsy based on molecular analysis of blood samples will complement existing clinical and histopathological parameters, leading to an improvement in patient outcomes.
The proposed project aims to exploit the extraordinary features of extracellular vesicles (EVs) to verify the hypothesis that circulating EVs could transport and transmit specific messenger RNAs (mRNAs) to recipient cells useful as predictive markers of progression from normal to proliferative lesions as well as from low risk, non-metastasizing forms to high risk, highly invasive carcinomas. We will also test the hypothesis that the overexpression of these mRNAs could be due to microRNAs (miRNAs) dysregulation. Finally, we will correlate mRNAs/miRNAs expression with anti-PD1 antibody therapy and patient outcome, proposing them as therapeutic markers.
