A new study has revealed how a single protein may drive two key features of cancer at the same time. Researchers found that MCL1 not only helps tumors survive but also regulates their energy use.
This discovery uncovers a hidden connection between two defining traits of cancer: the ability to avoid apoptosis (programmed cell death) and the rewiring of cellular metabolism.
MCL1: More Than a Survival Protein
MCL1 is produced at unusually high levels in many tumors. Previously, it was mainly known for helping cancer cells evade cell death as part of the Bcl-2 protein family.
The Dresden research team has now shown that MCL1 also interacts directly with mTOR, a central regulator of cellular metabolism. This means MCL1 actively controls how cancer cells manage their energy, linking survival and metabolic pathways.
Dr. Mohamed Elgendy explains, “MCL1 is much more than a survival factor. It intervenes in key growth and metabolic pathways, connecting two fundamental cancer mechanisms.”
A Newly Identified Signaling Pathway
The study revealed a direct connection between MCL1 and the mTORC1 complex across multiple cancer models.
This newly recognized pathway expands understanding of MCL1’s role and highlights potential new therapeutic targets.
Clinical Implications: Targeting MCL1 and mTOR
The researchers tested MCL1 inhibitors currently in clinical trials. They discovered that these drugs also block mTOR signaling, which is already a target in routine cancer therapy.
This finding suggests MCL1 inhibitors could provide dual benefits, attacking both tumor survival and metabolic processes simultaneously.
Solving the Cardiotoxicity Challenge
A major obstacle in previous MCL1 inhibitor trials was severe heart toxicity. The Dresden team identified the molecular cause and developed a dietary approach to reduce cardiac side effects.
They confirmed the protective effect in a humanized mouse model, paving the way for safer treatments.
Prof. Esther Troost comments, “This work advances our molecular understanding of cancer and demonstrates the clinical potential of targeted research.”
Prof. Uwe Platzbecker adds, “By solving the cardiotoxicity problem, this research shows how basic science can directly benefit patients and enable safer therapies.”
Toward Safer, More Effective Cancer Treatments
Overall, the study demonstrates that targeting MCL1 could simultaneously disrupt tumor survival and metabolism. With the new insights into cardiotoxicity, future therapies may be both more effective and safer for patients.
