Cellular changes that contribute to treatment resistance in melanoma can potentially be reversed using existing drugs, according to new research from Cornell University. Published on August 22, 2023, in the journal Advanced Science, the study reveals significant insights into the extracellular matrix (ECM) and its impact on cancer treatment efficacy.
The extracellular matrix, which serves as a supportive scaffold around cells, often becomes denser during cancer treatment. This thickening can hinder the effectiveness of therapies, leading to relapses in patients. Andrew White, associate professor in the Department of Biomedical Science at the College of Veterinary Medicine, emphasized the importance of understanding these mechanisms. “Melanoma patients usually respond very well to targeted therapy at first, but most eventually relapse as their tumors become resistant to treatment,” he stated.
The research team focused on the ECM’s role in treatment resistance, particularly changes observed in collagen, its main structural protein. The study’s first author, Chia-Hsin Hsu, explained that the team aimed to determine whether the ECM’s modifications were merely a side effect of therapy or if they actively contributed to drug resistance.
Key Findings on Treatment Resistance
The researchers made two pivotal discoveries. First, they demonstrated that the thickened ECM functions as a physical barrier. This density prevents cytotoxic T cells, which are essential for killing cancer cells, from effectively reaching the tumor site. “It changes the way we think about cancer treatment, from focusing only on the cancer cells themselves to understanding and treating the entire tissue environment around them,” Hsu noted.
Second, the team found that drugs capable of reducing or loosening the ECM allowed T cells to infiltrate the tumor more easily. Hsu described the findings as “thrilling,” noting that changes to the ECM could significantly alter the immune landscape of the tumor. Under microscopic observation, the researchers noted a more uniform distribution of cytotoxic T cells following ECM modification.
Implications for Future Treatments
These findings could pave the way for innovative treatments that combine existing targeted therapies or immunotherapies with agents designed to modify the ECM. Some of these ECM-modifying drugs are currently under investigation for their effectiveness in addressing tissue scarring. The potential repurposing of these drugs for melanoma treatment could lead to improved outcomes and reduced relapse rates.
The research team is now exploring whether other ECM molecules, beyond collagen, influence therapy resistance. By targeting these molecules, researchers hope to further reshape the tumor microenvironment and enhance the effectiveness of current treatments.
“Therapy doesn’t happen in isolation. It takes place within the constantly changing ecosystem of the tumor microenvironment, and the extracellular matrix is a vital part of that ecosystem,” Hsu concluded. This study underscores the notion that effective cancer treatment involves not only targeting cancer cells but also restoring the body’s environment to strengthen the immune system’s response.
The potential impact of this research highlights a significant shift in cancer treatment strategies, emphasizing the need for a holistic approach to combating diseases like melanoma.
