A phase 1 trial is testing a drug to restore the function of p53, the ‘guardian of the genome’, in specific cases
The p53 gene, known as the ‘guardian of the genome’, is a tumor suppressor gene that is mutated in more than half of all solid tumors in humans, affecting the function of the protein it encodes. However, there are no approved treatments capable of reactivating its function. A US team has tested a new drug in a phase 1 clinical trial that is capable of performing this function against a specific mutation, present in approximately 1% of solid tumors. After being administered to 77 people with different types of advanced or metastatic tumors, 20% showed a full or partial response, and the most common adverse effects were nausea or vomiting, according to a report published in NEJM.
McMillan - p53
Nigel McMillan
Director in Infectious Diseases and Immunology at Menzies Health Institute Queensland, Griffith University (Australia)
P53 is mutated in around 70% of all cancers and is therefore an attractive target for therapy, yet despite many years of research, it has proven difficult for researchers to develop drugs to. Part of the problem is there are many different mutations that affect this master regulator of cell survival. This paper presents promising results from an early phase clinical trial using a new drug, Rezatapopt, which targets one particular mutation. The trial showed 20% of patients had a response (at least 30% tumour shrinkage), and in a wide range of cancer types.
These results are highly impressive for such an early stage of trial in patients who had all undergone many different therapies before entering this trial. These are the most resistant and difficult cases, as their cancers were highly advanced.
This approach is attractive as Rezatapopt would be able to treat many different cancer types, and it can be taken orally, so it could be taken at home.
It offers a hope that we might finally have at least a partial solution to targeting the most important protein in cancer.
A larger trial is underway that will test if treatment will cure patients of their cancer.
Dumbrava et al.
- Research article
- Peer reviewed
- Clinical trial
- People
