An interdisciplinary research centre embedded within the Faculty of Life Sciences at The University of Manchester.

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Novel drug combination suppresses off-target effects of targeted MAP-kinase pathway therapy in melanoma

The MAP-kinase signalling pathway is stimulating cell growth and is deregulated in over 90% of malignant melanoma skin cancers. Therefore drugs targeting MEK as central kinase of this pathway are currently trialled in the clinical. However, responses are disappointingly lower than expected, and it is thought that up-regulation of counteracting signalling cascades as a direct response to MEK inhibition contributes to this phenomenon. We have discovered that in melanoma cells MEK inhibition by selumetinib (AZD6244, ARRY-142886), while efficiently suppressing tumour cell growth stimulates increased invasiveness.

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CLIC3 - a cancer cell’s helper

People die of cancer when cells from a tumour spread to other parts of the body, in a process called metastasis. In order for cancer cells to do this, they invade the ‘web’ of proteins and sugars fibres that surround cells in tissues, called the extracellular matrix (ECM). Cells are hooked onto the ECM by proteins called integrins, which bridge the cell to its environment. They can use these integrin ‘hooks’ to push and pull their way through the web of fibres. Cancer cells rely on integrins to invade the ECM and to spread to other parts of the body, so understanding how integrins work may aid the development of new drugs to prevent cell spreading. MORE ...