Breakthrough Study Links Cancer Metabolism to Key Protein, Offering New Therapeutic Pathways
A groundbreaking study published in Nature Communications reveals a previously unknown connection between cancer metabolism and the protein MCL1, potentially unlocking new avenues for treatment and addressing a critical safety concern with emerging cancer therapies. Researchers at the Technische Universität Dresden (TUD) have demonstrated that MCL1, long recognized for its role in preventing cell death, also actively controls the energy processes within tumor cells.
The research, led by Dr. Mohamed Elgendy’s group at the Mildred Scheel Early Career Center, fundamentally shifts our understanding of how cancer cells thrive. For years, scientists have recognized that cancer cells evade programmed cell death – a process called apoptosis – and exhibit dysregulated energy metabolism as hallmarks of the disease. This new work traces both of these characteristics back to a single molecular mechanism involving MCL1.
MCL1: More Than Just a Survival Factor
The protein MCL1 is frequently found in high levels in many types of cancer and has historically been viewed primarily as an inhibitor of apoptosis, belonging to the Bcl-2 protein family. However, the Dresden team’s findings reveal a far more complex role. They discovered that MCL1 directly influences mTOR, a central regulator of metabolism, effectively controlling the bioenergetics of cancer cells.
“Our findings show that MCL1 is much more than just a survival factor for tumor cells,” stated Dr. Elgendy. “The protein actively intervenes in key metabolic and growth signaling pathways, thereby linking two fundamental cancer mechanisms.”
The team identified a direct functional link between MCL1 and the mTORC1 complex across various cancer models. This newly identified signaling pathway expands the current understanding of MCL1’s function and suggests new targets for therapeutic intervention.
Implications for Cancer Therapeutics
The study also investigated the impact of MCL1 inhibitors, which are currently being evaluated in clinical trials as potential cancer treatments. Researchers found that these inhibitors also suppress mTOR signaling, a significant finding given that mTOR inhibitors are already established components of cancer therapy.
However, the development of MCL1 inhibitors has faced a major hurdle: severe cardiotoxic side effects observed in clinical trials led to the discontinuation of several studies. The Dresden researchers have now identified the underlying molecular mechanism responsible for this toxicity and, crucially, developed a dietary approach to significantly reduce the risk. This protective effect was validated using an innovative humanized mouse model.
“This work represents a significant advance in our understanding of the molecular basis of cancer,” said Prof. Esther Troost, Dean of the Carl Gustav Carus Faculty of Medicine at TU Dresden. “This high-ranking publication with enormous clinical potential once again demonstrates that the targeted support of outstanding young scientists, as carried out at the Mildred Scheel Center for Young Scientists, is a prerequisite for innovations and the cancer therapy of tomorrow.”
Prof. Uwe Platzbecker, Chief Medical Officer of the University Hospital Dresden, added, “This outstanding research work exemplifies how excellent basic research can create direct benefits for our cancer patients. Particularly significant from a clinical perspective is the solution to the cardiotoxicity problem of MCL1 inhibitors. The identification of the underlying mechanism and the development of a dietary protective approach can now pave the way for safer therapies.”
An International Collaborative Effort
The study was the result of a collaborative effort involving research groups and institutions across multiple countries, including Czechia, Austria, and Italy. Dr. Elgendy’s team in Dresden served as the lead partner, benefiting from the expertise of colleagues internationally.
The significance of the research was also recognized by the editors of Nature Communications, who highlighted the publication as one of the top 50 outstanding cancer research papers currently available on their “Editors’ Highlights” website.
Source: Technische Universität Dresden
Journal reference: https://www.nature.com/articles/s41467-025-66831-4
