Melanoma is one of the deadliest tumours known to humans with the highest propensity of all primary cancers to metastasize to the brain. Despite recent advances in targeted therapy for metastatic melanoma, the average survival of patients with metastatic brain disease remains less than 10 months. In search of a new therapeutic target, a recently established cell cycle regulator, FoxM1, that is found to be aberrantly expressed in many solid tumours, holds great promise in delivering more effective therapy.
FoxM1 is a signaling agent in the cell that is fundamental for normal cell growth and development. It is only present in growing cells and is switched off in mature cells. Abnormal gain of FoxM1 function has been found in many types of cancer and by targeting FoxM1, new treatment may be developed that could interrupt multiple signaling pathways critical for the development of brain metastases. With an across-the-board strategy to suppress cancer signaling while sparing other mature cells, anti-FoxM1 treatment may be more effective in halting the progression of brain metastases while producing less toxic effects.
Our project aims to evaluate the role of FoxM1 in the growth of melanoma cancer cells in a test tube environment. The overall goal is to characterise the expression of FoxM1 in melanoma and to determine its functional role in cell invasion, migration and angiogenesis. Our plan is to first acquire relevant in-vitro data through the use of human melanoma cell lines to assess the expression of FoxM1 in melanoma brain metastases. We will then conduct various tumorigenic assays with inhibition of FoxM1 to ascertain the effects of loss of function of FoxM1 on the development of various metastatic phenotypes. This basic research would form the groundwork for progressing to real life experiments in animals and ultimately to human clinical trials.