Dec 19, 2025
Dresden MSNZ Young Investigator Research Group has identified MCL1 as a central regulator of tumor metabolism
A recent study by the research group of Dr. Mohamed Elgendy, published in the prestigious journal Nature Communications, provides groundbreaking insights into key mechanisms of cancer. This scientific achievement was accomplished within the Mildred Scheel Young Investigator Research Group in Dresden. The study links, for the first time, two classic hallmarks of cancer: dysregulated cellular bioenergetics and evading programmed cell death (apoptosis).
At the heart of the research is the protein MCL1, previously known primarily for its anti-apoptotic role. The study reveals that MCL1 also plays a previously unknown central role in cellular metabolism: it regulates mTOR, a master controller of metabolism, directly influencing the bioenergetics of cancer cells. This work identifies MCL1 as the first common molecular effector connecting these two cancer hallmarks.
MCL1 and mTOR are among the most critical molecules in cancer biology. MCL1 is highly overexpressed in many tumor types and is a member of the Bcl-2 protein family, traditionally understood as downstream regulators of cell survival or death in response to stress signals. This study challenges that understanding by positioning MCL1 as an upstream regulator that actively intervenes in central signaling pathways - particularly mTOR signaling. The tumor-promoting effect of MCL1 is thus not solely due to its anti-apoptotic function but also its newly identified role in metabolic regulation.
The research provides compelling evidence for a direct link between MCL1 and mTORC1 across various cancer models, uncovering an entirely new signaling pathway. Beyond genetic analyses, the team also investigated the effects of pharmacological MCL1 inhibitors on tumors and healthy tissue. This allowed them to assess both the anti-cancer potential and possible side effects of these drugs.
The findings have immediate clinical implications. MCL1 inhibitors are considered promising new therapeutic options, with several currently in clinical development. The study reveals that these inhibitors unexpectedly also suppress mTOR signaling - a significant insight, as mTOR inhibitors are already routinely used in cancer therapy.
The study also sheds light on a previously unresolved issue: several clinical trials involving MCL1 inhibitors were halted due to cardiotoxicity. The Dresden researchers identified the underlying mechanism for this side effect and developed a dietary approach to significantly reduce heart toxicity. This protective effect was successfully validated in a state-of-the-art humanized mouse model, where the murine Mcl-1 gene was replaced with the human variant - a model that closely mirrors clinical effects.
The new insights and innovative preventive strategies could be pivotal in making MCL1 inhibitors safer and advancing their clinical use. This work opens up new avenues for developing a promising class of cancer therapeutics.
Contact details:
Mildred-Scheel Nachwuchszentrum (MSNZ P2 Dresden)
Medizinische Fakultät Carl Gustav Carus, TU Dresden
Fetscherstr. 74
01307 Dresden