We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.
Over half of all cancers contain mutations in a gene called TP53, also known as the “guardian of the genome”. Mutation of TP53 provides tumour cells with a growth advantage, and leads to resistance to chemotherapy and poor outcomes for patients. We have identified a potential “Achilles heel” in cancers with TP53 mutations. In this project we will establish a new paradigm for treating tumours with TP53 mutations that will be applicable to a large number of patients across all types of cancer.