Breakthrough strategy targets resistance in melanoma treatment


While significant progress has been made in melanoma treatment, resistance to current therapies remains a major challenge. NRASMUT melanoma, which accounts for approximately 30% of all melanoma cases, has shown limited response to MAPK inhibitors, with treatment failure in up to 80% of cases. To overcome this, the Villanueva lab focused on understanding the molecular mechanisms behind resistance in NRASMUT melanoma.


Dr Jessie Villanueva with lab colleagues. Credit: The Wistar Institute


Researchers at The Wistar Institute, led by Jessie Villanueva, PhD, have discovered a potential strategy for treating treatment-resistant melanoma by targeting the gene S6K2. Their findings [1], published in Science Translational Medicine, reveal that inhibiting S6K2 could enhance the therapeutic response in NRASMUT melanoma, a form resistant to MAPK inhibitors.


Melanoma, the deadliest form of skin cancer, continues to rise in incidence, particularly among individuals under 30.


Through a detailed analysis of genetic and molecular changes in response to MAPK inhibition, the team identified S6K2 as a key player in treatment resistance. Their research demonstrated that high expression of S6K2 was associated with poor patient outcomes and resistance to MAPK inhibitors. In the lab, silencing S6K2 effectively induced cell death in NRASMUT melanoma cell lines, revealing its potential as a therapeutic target.


Further investigation revealed that inhibiting S6K2 disrupted lipid metabolism in resistant melanoma cells, a crucial process for their survival. This insight led the team to explore additional treatment strategies. They found that targeting PPARα, another gene influenced by S6K2 inhibition, enhanced the anti-cancer effect. By combining fenofibrate (a PPARα activator) and DHA (Omega-3), the researchers successfully induced cell death in MAPKi- resistant melanoma cells.


Notably, many of the compounds tested, such as fenofibrate, are already used in humans for other purposes,


suggesting a low toxicity profile and a clear path for clinical translation. According to co-first author Brittany Lipchick, PhD, the combination treatment shows promise not only for its efficacy but also for its safety, offering hope for future clinical trials. Fellow co-first author Adam Guterres, PhD, emphasised that this work opens new avenues for treating melanoma without relying on highly toxic therapies. The findings offer an exciting direction for future melanoma treatments.


More information online: ilmt.co/PL/A74v


1. Selective abrogation of S6K2 maps lipid homeostasis as a survival vulnerability in MAPKi-resistant NRASMUT melanoma,, published in Science Translational Medicine.


Co-authors: Brittany Lipchick1 Chen1


Reyes-Uribe1 Yin1


Qin Liu1 Speicher1


, Delaine M. Zundell1 , Yulissa Tirado1


, Andrew V. Kossenkov1 , Aaron R. Goldman1


, Adam N. Guterres1


, Segundo Del Aguila1 , Subhasree Basu1 , Yiling Lu2


, and Jessie Villanueva1 , Hsin-Yi , Gordon B. Mills3


, Maureen E. Murphy1 .


, Patricia I. , Xiangfan ,


, David W.


1. The Wistar Institute, Philadelphia, Pennsylvania 19104 2. The University of Texas MD Anderson Cancer Center


3. Knight Cancer Institute, Oregon Health & Sciences University


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London Lab Live 2025


Study reveals how antibiotic-resistant Enterobacter hides in human cells


A groundbreaking study [1] has uncovered how the antibiotic-resistant bacteria Enterobacter can evade the immune system by hiding within human cells. This new research, published today in the Journal of Infection Diseases, reveals that Enterobacter species can remain dormant inside macrophages - key white blood cells that typically serve as the body’s first line of defence against infections - without triggering any immune response.


By avoiding detection, Enterobacter can survive despite the use of antibiotics, making infections difficult to treat. The findings highlight how Enterobacter infections, which can cause severe conditions such as urinary tract infections, pneumonia, and septicemia, continue to pose a serious threat to public health, even with appropriate treatment.


Taking place on 14–15 May at the ExCeL London, London Lab Live 2025 will bring together visionaries, thought leaders, and professionals from a wide range of lab-focused industries - including pharma, chemicals & materials, food & beverage, FMCG, academia, biotech, real estate, and more.


The event provides a dynamic platform for exploring, collaborating, and addressing the biggest challenges and achievements in building the lab of the future.


On the exhibition floor, attendees will find world-leading suppliers showcasing the latest technologies, software, and hardware, as well as an exciting start-up zone where smaller companies present groundbreaking innovations.


The conference program features eight themes, explored through diverse array of sessions led by industry experts.


London Lab Live offers unparalleled opportunities for networking, learning, and collaboration. Participants will connect with leading experts and gain insights into cutting- edge technologies shaping the future of innovation.


More information online:: ilmt.co/PL/XNk8 63650pr@reply-direct.com


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The study, conducted by the Valvano Lab Research Team at Queen’s University Belfast, was led by Professor Miguel A. Valvano, Chair in Microbiology and Infectious Diseases, along with Dr Georgiana Parau, Ms Hannah Parks, Ms Amy Anderson, and Dr Inmaculada Garcia-Romero. Professor Valvano explained: “This research fills a crucial gap in our understanding of how Enterobacter species evade the immune system. The ability to persist inside macrophages means that these bacteria can evade both antibiotics and the body’s natural defences.”


The breakthrough could lead to new treatment strategies that target intracellular bacteria more effectively, potentially reducing the mortality rate associated with these infections.


The research was funded by the Biotechnology and Biological Sciences Research Council.


More information online: ilmt.co/PL/4yDl Professor Miguel A. Valvano. Credit: Queen’s University Belfast


1. Clinical Isolates of Antimicrobial-Resistant Enterobacter Species Can Persist in Human Macrophages Without Replication and Overt Cellular Cytotoxicity published in The Journal of Infection Diseases


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