Uterine leiomyosarcoma is a poorly understood cancer that doesn’t respond well to current treatment methods. This project is working towards changing that by using powerful new techniques to understand more about how this cancer grows and spreads, and by testing a promising new class of drugs for their effectiveness in treating uterine leiomyosarcoma.
Molecular characterisation of primary uterine leiomyosarcoma and preclinical investigation of response to non-genotoxic activators of p53 via the MDM2/p53/PPM1D signalling network
Uterine leiomyosarcomas (uLMS) are relatively rare aggressive cancers of the uterus which arise from the smooth muscle cells that make up the wall of the uterus. They respond poorly to current treatments and have a high risk of recurrence and death regardless of how soon they are diagnosed. There is a lack of knowledge about what changes have happened in the muscle cells to make them grow out of control in this type of cancer.
Our aim is to use powerful new techniques which have been developed to search for mutations and changes of gene expression that drive the growth and spread of the tumour cells. These changes will vary between individual patients.
A new class of drugs that we have been developing are called MDM2 inhibitors. These drugs target a gene in uLMS and we have strongly convincing pilot results showing that uLMS cancer cells are particularly sensitive to this new class of drugs. One of the advantages of MDM2 inhibitors is that unlike conventional chemotherapy they do not damage DNA and are therefore referred to as “non-genotoxic”. As part of this project we will test combination treatments with MDM2 inhibitors and other novel non-genotoxic drugs for their effectiveness in uLMS.