Scientists uncover a hidden switch that helps cancer cells thrive
Scientists have uncovered evidence that two defining features of cancer are driven by the same underlying molecular process. These
Scientists have uncovered evidence that two defining features of cancer are driven by the same underlying molecular process. These features include cancer cells avoiding apoptosis (a form of programmed cell death) and altering how they produce and use energy. Until now, these processes were largely studied separately.
The research centers on a protein called MCL1, which is produced at unusually high levels in many types of tumors. MCL1 has long been viewed mainly as a protein that helps cancer cells avoid death and is part of the Bcl-2 protein family. The Dresden research team has now shown that MCL1 also directly affects mTOR, a major regulator of cellular metabolism. By influencing mTOR, MCL1 helps control how cancer cells generate and manage energy. This marks the first time MCL1 has been identified as an active controller of major signaling and metabolic pathways.
“Our findings show that MCL1 is much more than just a survival factor for tumor cells,” says Dr. Mohamed Elgendy. “The protein actively intervenes in key metabolic and growth signaling pathways, thereby linking two fundamental cancer mechanisms.”
By examining multiple cancer models, the researchers discovered a direct functional connection between MCL1 and the mTORC1 complex. This newly identified pathway reshapes current understanding of what MCL1 does inside cancer cells and points to new possibilities for treatment strategies that target this connection.
Alongside genetic studies, the team also tested drugs designed to block MCL1. These inhibitors are already in clinical development as potential cancer treatments. The researchers found that these drugs also reduce mTOR signaling. This is especially important because medications that target mTOR are already widely used in cancer care, making the overlap between these pathways highly relevant for clinical practice.
One of the most impactful discoveries addressed a long standing challenge. Several clinical trials of MCL1 inhibitors were previously halted because patients experienced severe damage to the heart. The Dresden team identified the molecular cause of this cardiotoxicity for the first time. Based on this insight, they developed a dietary strategy that significantly reduced heart damage. This protective effect was confirmed using an advanced humanized mouse model.
“This work represents a significant advance in our understanding of the molecular basis of cancer,” says 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, adds: “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.”
The study was made possible through collaboration among multiple research teams and institutions. Dr. Mohamed Elgendy’s group in Dresden led the project, with contributions from partners in Czechia, Austria, and Italy.
The findings also drew attention from the journal Nature Communications. Editors selected the paper for the “Editors’ Highlights” section, which showcases the 50 most notable cancer studies currently published, underscoring the broad significance of the work.
