New Insights into MCL-1 Protein Offer Hope for Safer Cancer Treatments

Recent research led by the Walter and Eliza Hall Institute of Medical Research (WEHI) has unveiled a dual role of the MCL-1 protein, which could significantly impact the development of cancer therapies. This landmark study, published in the journal *Science* on July 8, 2025, indicates that MCL-1 not only prevents cell death but also supports cellular energy production, a finding that may help mitigate the severe side effects often associated with existing cancer treatments targeting this protein.

MCL-1 has emerged as a promising target for cancer drug development due to its critical functions in cell survival and metabolism. According to Dr. Kerstin Brinkmann, a researcher at WEHI and the study's first author, this research represents the first time the metabolic role of MCL-1 has been demonstrated in a living organism, marking a fundamental shift in understanding its biological functions. "It's a fundamental shift in how we understand what this protein does," said Dr. Brinkmann. This revelation is expected to pave the way for smarter, more targeted therapies that can selectively kill cancer cells while sparing healthy tissue, particularly in high-energy-demand organs such as the heart and liver.

The implications of these findings are substantial. Professor Andreas Strasser, a co-senior researcher and WEHI laboratory head, emphasized that successfully directing MCL-1 inhibitors to tumor cells while avoiding healthy tissues could enhance the efficacy of cancer treatments and reduce their toxicity. Current clinical trials of MCL-1 targeting drugs have reported significant side effects, primarily in the heart, which have limited their application in cancer therapy. "If we can direct MCL-1 inhibitors preferentially to tumor cells, we may be able to selectively kill cancer cells while sparing healthy tissues," Professor Strasser noted.

Furthermore, the study opens avenues for improved combination therapies. By elucidating the distinct pathways influenced by MCL-1, researchers can design more effective dosing strategies and combine MCL-1 inhibitors with other treatments to minimize adverse effects. Professor Marco Herold, CEO of the Olivia Newton-John Cancer Research Institute (ONJCRI) and co-senior researcher on the project, stated, "This work exemplifies the power of discovery science. It shows why we need to support curiosity-driven science. That's where the big insights come from."

In addition to its implications for cancer treatment, the research highlights a potential link between MCL-1 and rare metabolic diseases, such as mitochondrial disorders that affect infants. These conditions are often fatal due to insufficient energy production in cells, and the findings suggest that MCL-1 could play a previously unrecognized role in these diseases, providing a new target for future therapies.

The successful collaboration among experts in cancer biology, metabolism, developmental biology, and gene editing has been pivotal in this study. As Professor Strasser remarked, "This kind of discovery only happens when you have the right mix of people and expertise. This is a powerful example of how fundamental science drives future medical breakthroughs."

The study, titled "Relative importance of the Anti-Apoptotic versus Apoptosis-Unrelated Functions of MCL-1 in vivo," is expected to significantly influence future drug development strategies aimed at targeting MCL-1 and similar proteins. With ongoing clinical trials and further research, the potential for safer and more effective cancer therapies continues to expand.

In summary, the WEHI-led study not only enhances the understanding of MCL-1's functions but also sets the stage for innovative approaches to cancer treatment that prioritize patient safety and minimize side effects. As researchers continue to explore the therapeutic potential of MCL-1, the findings could herald a new era in cancer treatment, offering hope to patients and healthcare providers alike.