Researchers have just revealed that a protein called MCL1, already known to help cancer cells avoid death, also orchestrates the management of their energy. This dual role opens up new perspectives for understanding how tumors grow and resist therapies.
Until now, the MCL1 protein was mainly studied for its ability to protect tumor cells from apoptosis, a natural self-destruction mechanism. Found in large quantities in many cancers, it was part of the Bcl-2 protein family. Its function seemed limited to this single aspect of cell survival, making it an interesting target for therapies aimed at eliminating diseased cells more effectively.
Illustrative Image Unsplash
However, the Dresden team has revealed a novel aspect of MCL1. In reality, this protein interacts directly with mTOR, an essential regulator of cellular metabolism. By influencing mTOR, MCL1 helps cancer cells adapt their energy production and consumption according to their needs. This dual function makes MCL1 a major player in two fundamental processes of cancer, thus linking mechanisms that were until now considered separate.
This discovery has immediate practical implications. MCL1 inhibitors, currently being tested in clinical trials, have been shown to also block mTOR signaling. Consequently, a single treatment could target both tumor survival and metabolism. Furthermore, this approach could improve the effectiveness of existing therapies, as mTOR inhibitors are already used against certain cancers.
However, a major obstacle had hindered the development of MCL1 inhibitors: their cardiac toxicity. Several clinical trials had to be stopped due to serious side effects on the heart. The research team has identified for the first time the molecular mechanism behind this problem. Based on this, they have developed a simple dietary approach that can significantly reduce cardiotoxicity, as confirmed by tests on a humanized mouse model.
These advances are the result of an international collaboration involving institutes from the Czech Republic, Austria, and Italy. Dr. Mohamed Elgendy, the study's lead, indicates that MCL1 is much more than just a survival factor; it actively participates in signaling pathways related to growth and metabolism. This work demonstrates the value of fundamental research for designing safer and more effective treatments.
The clinical prospects thus seem encouraging. By solving the problem of cardiac toxicity, this study could allow the development of MCL1 inhibitors to be relaunched. This would pave the way for new therapeutic combinations targeting several weaknesses of cancer cells simultaneously, which represents a promising path for patients with resistant cancers.