Study reveals processes important for skin cancer aggressiveness and identifies two classes of drugs that may block them

Researchers have discovered that the most aggressive melanomas, the deadliest form of skin cancer, overactivate two key processes in mitochondria, the components of cells that provide energy. Blocking these pathways with currently available drugs effectively killed melanoma cells. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

By mapping the proteins expressed in 151 tumor and normal skin samples, investigators found that the most aggressive melanomas hyper-activate the machinery that builds mitochondrial proteins and the mitochondrial system that turns nutrients into energy.

Remarkably, blocking these pathways effectively halted or killed melanoma cells cultured in lab dishes. Two types of drugs accomplished this: antibiotics—originally designed to block bacterial protein synthesis machinery, which closely resembles the machinery found in mitochondria—and specialized energy-production inhibitors. Importantly, non-cancerous skin cells remained mostly unaffected, highlighting the safety and specificity of these treatment approaches.

“This discovery identifies melanoma's excessive reliance on mitochondrial energy as its Achilles’ heel, revealing a therapeutic vulnerability that we can exploit with existing drugs,” said senior author Jeovanis Gil, PhD, of Lund University in Sweden. “By pairing mitochondrial blockers with today’s standards of care, we may cut off a major escape route that cancers use to resist therapy and come back.”

Dr. Gil added that the mitochondrial-protein signature his team discovered can be measured in routine biopsy material and could serve as a biomarker to identify patients most likely to benefit from mitochondrial-targeted add-on therapies. By enabling clinicians to match treatments to each patient’s tumor biology, these findings mark a step forward for precision medicine in melanoma. Moreover, because mitochondrial rewiring fuels resistance across many cancers, success in melanoma could open the door to similar personalized combination strategies in other hard-to-treat cancers. 

Additional information
NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the CANCER Newsroom upon online publication. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com

Full Citation:
“Mitochondrial Proteome Landscape Unveils Key Insights into Melanoma Severity and Treatment Strategies.” Yonghyo Kim, Viktória Doma, Uğur Çakır, Magdalena Kuras, Lazaro Hiram Betancourt, Indira Pla, Aniel Sanchez, Yutaka Sugihara, Roger Appelqvist, Henriett Oskolas, Boram Lee, Jéssica Guedes, Gustavo Monnerat, Gabriel Reis Alves Carneiro, Fábio CS Nogueira, Gilberto B. Domont, Johan Malm, Bo Baldetorp, Elisabet Wieslander, István Balázs Németh, A. Marcell Szász, Runyu Hong, Krzysztof Pawłowski, Melinda Rezeli, Ho Jeong Kwon, József Tímár, David Fenyö, Sarolta Kárpáti, György Marko-Varga, and Jeovanis Gil. CANCER; Published Online: June 23, 2025 (DOI: 10.1002/cncr.35897).
URL Upon Publication: http://doi.wiley.com/10.1002/cncr.35897

Author Contact: press@med.lu.se

About the Journal
CANCER is a peer-reviewed publication of the American Cancer Society integrating scientific information from worldwide sources for all oncologic specialties. The objective of CANCER is to provide an interdisciplinary forum for the exchange of information among oncologic disciplines concerned with the etiology, course, and treatment of human cancer. CANCER is published on behalf of the American Cancer Society by Wiley and can be accessed online. Follow CANCER on X @JournalCancer and Instagram @ACSJournalCancer, and stay up to date with the American Cancer Society Journals on LinkedIn.

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