The most aggressive melanomas may hyperactivate two key processes in mitochondria, according to a novel study, and blocking these pathways with currently available drugs may eliminate melanoma cells, explained investigators. These findings were published by Kim et al in the journal Cancer.
Researchers mapped the proteins expressed in 151 tumor and normal skin samples, and found that the most aggressive melanomas hyperactivated the machinery responsible for building mitochondrial proteins as well as the mitochondrial system turning nutrients into energy. Notably, blocking these pathways with antibiotics and specialized energy-production inhibitors effectively halted or killed melanoma cells cultured in laboratory settings. The antibiotics were initially designed to block bacterial protein synthesis machinery, which closely resembled the machinery found in mitochondria. Further, the researchers emphasized that noncancerous skin cells remained mostly unaffected—highlighting the safety and specificity of these treatment approaches.
The mitochondrial-protein signature discovered in the study 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 physicians to match treatments to each patient’s tumor biology, the findings indicated advances in precision medicine for the treatment of melanoma.
“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,” underscored senior study 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,” he continued.
The researchers concluded that because mitochondrial rewiring fuels treatment resistance across many cancer types, the novel treatment strategy could pave the way for similar personalized combination strategies in other difficult-to-treat cancers.
Disclosure: For full disclosures of the study authors, visit acsjournals.onlinelibrary.wiley.com.
