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Project

Hypoxia-driven signaling pathways in the progression of cutaneous malignant melanoma.

Cutaneous malignant melanoma (CMM) develops from the malignant transformation of melanocytes, neuroectodermal cells residing in the epidermal basal layer that provide pigmentation to the skin through the synthesis of melanin. Whereas melanoma in its earliest stages (e.g. radial or limited invasion phase) is still curable, once it has disseminated (e.g. at the stage of metastatic melanoma) it becomes a fatal disease also due to its notorious chemoresistance (1). In fact, although CMM represents a minority (4%) of all dermatological cancers it is responsible for 80% of the mortality due to skin cancers and the survival rate of patients with metastatic CMM is only 12% over 5 years. As the incidence of CMM is still rising, the development of new therapeutic strategies for this extremely aggressive tumor with high mortality is an urgent need and requires a deeper insight into the molecular mechanisms underlying this disease. In the proposed project, we plan to unravel the intracellular signaling pathways mediated by UVB and hypoxia in CMM progression. The specific aims of this study are; 1) to underscore the signaling components that underlie the hypoxia-mediated survival and the UVB-mediated cell death in CMM 2) to reveal the functional relevance of the induction of HIF-1alfa by UVB (normoxia) or hypoxia in CMM development and progression.
Date:1 Jan 2008 →  31 Dec 2011
Keywords:Cell signalling, Anti-cancer therapy, Autophagy, Melanoma, Hypoxia, Signaling pathways
Disciplines:Morphological sciences, Oncology, Dermatology, Biochemistry and metabolism, Medical biochemistry and metabolism