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The role of UV exposure and novel compounds on the immunogenicity and genotoxicity of skin cancer

Project Description

The major aims of this project are to investigate the effect of UV in the development of different skin cancers compared to spontaneously regressing precancerous lesion, keratoacanthoma; and the effect of a novel compounds such as the structurally modified retinoic acid in the treatment of skin cancers and other cutaneous lesions.

Keratoacanthoma (KA) is cutaneous neoplasia and is considered to be a benign variant of squamous cell carcinoma. It is thought to be preferably derived from hair follicle cells, particularly on sun-exposed skin. KA is characterized by self-limiting growth and involution; therefore, the life cycle from origin to spontaneous regression takes about 4 to 6 months in the majority of cases (Schwartz, 1994, Watanabe et al.,2015). The ability of KA to grow and regress mirrors hair follicle cycling during physiological regeneration (Ramselaar. et al., 1980).

Both the hair follicle as well as regressing tumours represent a significant model for identifying physiological mechanisms that promote tumour regression, thus providing potential new avenues for the development of targeted therapy for non-regressing tumours. Strong arguments support classifying keratoacanthoma as a variant of invasive Squamous Cell Carcinoma (SCC) (Gleich et al., 2016). There are similarities between KA and SCC nevertheless neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to the involvement of distinct pathogenesis (Watanabe et al., 2015). Gleich et al. suggested that TGFβ signalling is the leading cause of familial KA, (Gleich et al., 2016).

In this project, the first aim is to investigate the pathways involved in the progression of the tumour and also self-regression of KA. Moreover, the differences between KA and other skin cancers will be studied.

Funding Notes

This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee also applies in addition to tuition fees.

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