There is one gene which is mutated more than any other in cancer. This gene is called p53, but it is often referred to as the 'guardian of the genome' because of its vital role in controlling DNA repair and cell division. A project our Curestarters helped fund over ten years ago allowed Professor John Spencer to carry out vital research about p53. Thanks to research by Professor Spencer and others a new cancer treatment called Rezatapopt, targeting a particular p53 mutation, has now entered clinical trials.
I am delighted to see that Rezatapopt has now entered clinical trials for patients with advanced solid tumours, and I hope that in the future it will go on to help many more cancer patients. New treatments like this wouldn’t be possible without discovery research so thank you to the Curestarters who helped us make breakthroughs that others have built upon to make their important discoveries.
Since p53 is mutated in approximately half of all cancers, it is an appealing target for cancer treatments and has been the focus of much research. Over a decade ago, a trio of incredible scientists needed funding for cutting-edge research exploring the idea of treating cancer by targeting a specific p53 mutation. Fortunately, that's exactly the kind of research that our Curestarters choose to support.
Professor John Spencer, a medicinal chemist in Sussex, teamed up with p53 experts Sir Alan Fersht and Dr Andreas Joerger in Cambridge (now in Frankfurt and also funded by the German Research Foundation) to investigate a p53 mutation called Y220C, which occurs in at least 30 cancer types and around 100,000 cancer patients every year.
This mutation makes p53 'wobbly' - meaning it can't do its job of protecting our cells. The team identified 'pockets' on the Y220C protein which potential drugs could connect to, along with ways to boost this connection. This work, along with research from other teams, laid the groundwork for new treatments that could work by stabilising the p53 Y220C mutant (see image showing the surface of the Y220C mutation with a small molecule stabilizer bound to it). By restoring the regular or 'wild type' version of the protein, treatments could reactivate p53’s protective functions in the mutated tumor cells, thereby stopping their unregulated growth and eventually killing them.
And now a new treatment called Rezatapopt has been created by PMV Pharma - the first drug ever to specifically target this mutation.
Clinical trials have begun, involving patients with advanced solid tumours, including ovarian, lung, breast, and endometrial cancer. These trials will study the effectiveness of Rezatapopt in treating these cancers - both on its own and in combination with other therapies.
If they are successful, Rezatapopt will become a treatment option for thousands of cancer patients worldwide.
It takes a lot of time, resource, and expertise to get a breakthrough from bench to bedside. Thanks to our Curestarters - researchers like Professor John Spencer and supporters like you - we are continually finding out more and more about how cancer behaves, and how to stop it in its tracks.
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