Cellular Signalling in Melanoma Skin Cancer
Cancer is a class of diseases that is initiated by uncontrolled growth and survival, and progresses through invasion and metastasis. Melanoma is a skin cancer that develops from abnormal moles; it is the skin cancer with the highest mortality rate mostly because melanoma cells are extremely invasive and tend to metastasise early, and advanced tumours are highly resistant to conventional cancer treatments.
A major problem in the treatment of melanoma is posed by the cellular heterogeneity within the tumour tissue - including genetically differing cancer cells and other cell types in the tumour microenvironment - because:
1. The presence of individual genetically differing cells within a tumour always allows some cells to escape from the effect of a cancer drug, and this can result in the development of resistance to the treatment, or even worse in the generation of more aggressive tumour cells.
2. The communication between the individual cells within a tumour and their interaction with the tumour microenvironment contributes to the dissemination and invasion of cancer cells away from the primary tumour site. Moreover, it also enables them to escape drug effects in the first place, which is reflected in a low response to an otherwise efficient drug.
Work in my laboratory aims to address these two major issues.
1. We want to reveal the impact of tumour heterogeneity and microenvironment on the overall drug response of a tumour in order to improve initial responses and reduce the occurrence of resistance.
2. We want to understand how the communication between cancer cells and the tumour microenvironment regulates the invasive behaviour of individual cancer cells.
The lab uses reconstituted 3D cell-culture models and in vivo live cell imaging of tumour cells in zebrafish, as well as cell biological and protein-biochemical approaches to study the relevant cellular processes at the molecular level. Furthermore we are performing high-throughput siRNA and drug screens using high content imaging techniques in 2D and 3D. In particular we are investigating the role of the melanoma specific fate-decision regulator MITF (Microphthalmia transcription factor), and its link to the RAF/MEK/ERK MAP-kinase pathway and SRC kinases, and other cellular signalling cascades (e.g. Cadherin/catenin and TGFb signalling).