Study Uncovers the Mechanism Behind Melanoma's Resistance to Treatment

The effect of targeted therapy in treating malignant melanoma is often lost over time. A new study showed that a factor secreted by tumor cells is responsible for the resistance. The findings, which appeared in Cell Reports Medicine, could pave the way for more effective therapies.

Despite recent progress in effective therapies for melanoma, the tumors of many patients are either resistant from the outset or become so during the course of treatment. “It is therefore crucial to understand the mechanism behind resistance development in melanoma,” said Lukas Sommer, professor of stem cell biology at the Institute of Anatomy at the University of Zurich, via a press release.

The researchers utilized innovative fine-needle biopsy to sample tumor cells before and during therapy. This approach allowed the researchers to analyze each cell individually. The patients providing the samples were undergoing targeted cancer therapy for malignant melanoma, which inhibits signaling pathways for tumor formation.

Notably, the study found that in the POSTN gene—a secreted factor that plays an important role in resistant tumors—patients with rapidly progressing disease despite treatment showed increased POSTN levels. Moreover, the findings showed that microenvironment of these tumors contained a larger number of a certain type of macrophage. Subsequent to further analysis, the researchers were able to show how the interaction of increased POSTN levels and this type of macrophage triggers resistance.

“The study highlights the potential of targeting specific types of macrophages within the tumor microenvironment to overcome resistance,” Prof. Sommer said. “In combination with already known therapies, this could significantly improve the success of treatment for patients with malignant melanoma.”