Actinic keratoses (AK) are regarded as early in situ carcinomas and bear the potential to progress into an invasive cutaneous squamous cell carcinoma (cSCC). In industrial countries, increasing incidence of keratinocyte cancers and AKs in particular has been observed. AKs are considered as chronic diseases with increasing costs to the health service as the prevalence continues to rise.
Clinically, AKs present as macules, papules, or hyperkeratotic plaques with an erythematous background on photoexposed areas.
Single AK was found to have HPVs in healthy looking and lesional skin of affected patients. AK patients express in their skin HPV5,-38,-76,-110,-120,-4 and SD2, some of which are oncogenic in vitro and in animal models.
The microRNA (miRNA) profile of AK samples showed that several miRNAs regulating specific gene expression involved in cancer progression are modulated in AK compared to healthy skin.
Extracellular membrane vesicles (EVs), as a vehicle-like device, appear to be an important multifaceted regulator of tumor progression. EVs derived from cancer cells, released in greater numbers than from normal proliferative cells, can modulate immune responses, transfer oncogenic proteins and nucleic acids, reprogram stromal cells and transfer the drug-resistance phenotype. There is little mechanistic knowledge of EV-related events in cancer i.e. the mechanism(s) of cargo selection and release, and their molecular target(s) in cytoplasm and nuclear compartment of host cells.
This project will analyze the features of AK and cSCC clinical samples focusing on the detection of selected ß and y-HPVs in a liquid biopsy approach to identify virus-associated biomarkers of cancer progression useful to develop both diagnostic tests and targeted therapies. In addition, cell free circulating- and EV-associated miRNAs, will be assessed on blood samples of cSCC patients admitted to anti-PD-1 treatment, to identify possible therapeutic outcome predictive biomarkers.
