Alternative Approach to Proliferation Pathway Suppression in Human Cancers
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Cancer is a disease driven by complex genetic abnormalities. The ultimate outcome of these complex genetic disorders is uncontrolled cell proliferation. There are two major cellular proliferation and survival signalling pathways which are RAS-RAF- MEK-ERK and PI3K-AKT-mTOR proliferation-survival pathways. These proliferation-survival cell signalling pathways receive, carry and transfer important cell signals to the nucleus where the major transcription changes required for cell proliferation and survival occur. In normal cells, this proliferation cell signalling process is controlled, but this process becomes uncontrolled in cancer cells due to complex genetic changes like genetic mutations. One such genetic mutation is the BRAF V600E mutation which transforms the BRAF kinase into an auto-activated kinase. As a result, the RAS-RAF-MEK-ERK proliferation-survival pathway becomes truncated and auto-activated BRAF kinase continuously sends proliferation-survival signals to the nucleus through downstream MEK-ERK signalling molecules. Therefore, BRAF V600E mutated cells proliferate without control, invade & damage surrounding tissues and metastasise all over the body.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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Proliferation-survival cell signalling pathways