A breakthrough study from Australia’s Walter and Eliza Hall Institute of Medical Research (WEHI) has provided important insights into why certain promising cancer treatments lead to severe side effects, a long-standing challenge in oncology.
The research, published in the journal Science, centres on the protein MCL-1 — widely regarded as a key target in cancer drug development.
MCL-1 is known for its role in preventing cancer cell death. However, the study reveals that this protein also plays a critical role in supplying energy to healthy cells, especially those in organs with high energy needs such as the heart and liver.
This dual function means that drugs designed to inhibit MCL-1 can unintentionally damage vital tissues, explaining the serious side effects observed during clinical trials.
New understanding of MCL-1’s metabolic role
Dr Kerstin Brinkmann, the study’s first author, highlighted the significance of their findings: “While previous studies in cell cultures suggested MCL-1 might have a role in metabolism, it wasn’t clear whether that held true in living organisms. Our research confirms its essential function in energy production across healthy tissues.”
The research represents the first demonstration of MCL-1’s metabolic function in live organisms and marks a key shift in how scientists understand the link between cancer cell death and cellular metabolism.
This insight paves the way for new treatment strategies that aim to strike a better balance between destroying cancer cells and protecting healthy tissue.
Andreas Strasser, Head of the WEHI laboratory, explained that these findings could help shape the next generation of cancer drugs.
“If we can develop methods to deliver MCL-1 inhibitors more precisely to tumour cells while sparing healthy organs, we could reduce toxicity and improve patient outcomes,” he said.
The team also believes this research will inform smarter combination treatments — where careful pairing and dosing of MCL-1 inhibitors with other therapies could reduce side effects without compromising effectiveness.
This new understanding could transform how pharmaceutical companies design cancer treatments.
With targeted strategies that protect vital organs, the hope is that future therapies will offer both efficacy and safety, improving survival rates while preserving patients’ quality of life.
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