Uterine leiomyosarcomas (uLMS) are rare cancers that grow in the muscle wall of the womb. They are very hard to treat and little is known about what makes them grow and spread. The researchers wanted to look for changes in the genes of the tumour cells. These might suggest cancer drugs which could be used for uLMS, and discover ways new drugs might work.
Before this study the team were working on new treatments called MDM2 inhibitors. These drugs are exciting as they do not cause as much damage to the rest of the body as chemotherapy or radiotherapy. The team wanted to test whether the MDM2 inhibitor drugs would work in uLMS.
How will this project tackle this challenge?
To start with, the team used uLMS samples to build a genetic picture. They then tested cells in the laboratory with existing cancer drugs and drug combinations including MDM2 inhibitors.
Was it successful?
Yes! The team found promising results that the uLMS cells were very sensitive to MDM2 inhibitors. However, they also found that a particular protein called WIP1 made the drug work less well. By using a different drug to stop WIP1 alongside the MDM2 inhibitor, the team got excellent results and hope to extend this to a clinical trial in sarcoma patients.
There was also good news with the testing of existing cancer drugs. They found that combining two drugs (PARP and MTOR inhibitors) was much more successful with treating uLMS cells than with either drug by itself. Excitingly the individual drugs could also be used in smaller doses which should reduce side effects. Similar success was achieved by combining MTOR and MDM2 inhibitors.
What this means for people affected by sarcoma
This study has improved the understanding of the rare sarcoma uLMS but also provided great hope for new drug treatments. The ultimate aim is to personalise treatment for uLMS patients based on the genetic work started with this project.
The study also led to the creation of a biobank for uLMS, where patient samples are stored and can be used by researchers into the future. This is particularly important for rare sarcomas like uLMS as not many samples are collected each year. This vital resource could expand the work already done and lead to new breakthroughs.
This study has improved the understanding of the rare sarcoma uLMS but also provided great hope for new drug treatments.