THE ESSENTIAL
- In France, the estimated number of new cases of glioblastoma was 3,481 for the year 2018.
- This brain cancer causes headaches, nausea, vomiting, strength deficits and seizures.
- Dysfunction of the circadian clock is frequently associated with metabolic diseases.
Glioblastoma is the most common malignant brain tumor in adults. After diagnosis, patients suffering from this cancer affecting astrocytes (ie cells of the central nervous system) only survive an average of 15 months. Despite more than two decades of research into the causes and treatments of glioblastoma, this life-threatening prognosis has not improved.
“In the vast majority of patients, the cancer comes back”, said Steve Kay, professor at the University of Southern California (USA). He thinks the tumor is coming back because a small number of cancer cells are still present following surgery, chemotherapy and radiotherapy. These cancer cells would hijack the body’s circadian clock mechanisms, allowing them to spread faster and resist the effects of chemotherapy and radiotherapy.
Brain cancer: the discovery of the drug molecule “SHP656”
Recently, Steve Kay and a team of researchers revealed that circadian clock proteins, which help coordinate changes in body functions over the course of a day, may play a key role in growth and spread of this brain cancer.
In a study published in the journal Proceedings of the National Academy of Sciences (PNAS)they identified a new class of small molecule, called “SHP656”, that can target circadian clock proteins and prove effective in treating glioblastoma. “It is a powerful molecule”said Steve Kay in a statement.
To achieve this discovery, the authors created and tested thousands of molecules capable of binding to circadian clock proteins inside cancer cells and potentially neutralizing them. They used several techniques, including artificial intelligence (AI), to determine which molecule was best suited to fight glioblastoma. The algorithms made it possible to pinpoint the “SHP656” molecule.
Glioblastoma: the “SHP656” molecule would reduce the growth of cancer cells
The scientists then tested the effectiveness of the “SHP656” molecule using stem cells taken from patients affected by glioblastoma. They observed that “SHP656” reduced the growth of cancer cells.
“We find that the molecule acts differently on healthy brain cells than on tumor cells. It was a real leap forward in our understanding of how we can develop drugs that target circadian clock proteins.” , said Steve Kay.
Currently, this treatment is being evaluated in a clinical trial. Steve Kay and his colleagues are also investigating its usefulness in treating colorectal cancer, liver cancer, and acute myeloid leukemia.