New Perspectives on Melanoma_ The Role of PAX3

We hypothesise that its activity drives the cells

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Unformatted text preview: ly expressed in melanoma, and its expression correlates with melanoma staging/progression [21‐26]. While PAX3 is known to contribute to melanoma cell survival [27,28], it is not known whether it continues to control pathways of differentiation, migration and proliferation in melanoma cells as it does during embryonic development, and whether this contributes to melanoma progression and metastatic spread. The analogy between developmental processes and tumourigenesis, and the pivotal role that PAX3 has during melanocyte development, has instigated us to further investigate PAX3 involvement in melanoma development/progression. Furthermore, due to a lack of conclusive information on the precise role of PAX3 in normal adult epidermal melanocytes, the significance of its continued expression in normal melanocytes as they progress through to melanoma is unknown. Further studies are required to determine the causal relationship between PAX3 and tumourigenesis and to determine the downstream molecular mechanisms involved in melanoma metastasis. Significance of the study For melanoma patients complete surgical removal of a primary lesion is the first line of treatment and this remains the most successful therapy [29]. Current therapies for advanced melanomas have limited success, but new targeted therapies are proving more successful [30‐34]. Identification of the key regulators of melanoma progression would provide a tool for development of more effective therapies to halt metastatic spread. 2 Chapter I – Thesis Overview PAX3 controls maintenance of the undifferentiated cell state, as well as proliferation, migration and survival, throughout melanocyte development and maturation. PAX3 might act similarly during melanoma‐genesis, ie as a key intrinsic factor driving melanoma development and progression. We hypothesise that its activity drives the cells towards an undifferentiated proliferative motile state, which predisposes them to an aggressive phenotype upon malignant transformation....
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