Triggering cell death in metastatic melanoma could pave the way for new oncological treatments. A study, recently published in the journal Natureoffers new ways to understand cancer and its vulnerabilities and suggests that certain protein inhibitors could represent effective treatments against this disease.
Melanoma metastasis remains one of the biggest challenges in oncology, but researchers have discovered a possible weakness of these aggressive cells.
A team from the Harvard TH Chan School of Public Health has identified a protein essential for the survival of tumor cells that spread to lymph nodes, opening the way to a new class of anticancer treatments.
The study, published Wednesday in the journal Natureshow that metastatic melanoma cells rely on ferroptosis suppressor protein 1 (FSP1) to avoid cell death. When this protein is inhibited, tumor cells can no longer counteract oxidative stress and die through a process called ferroptosis – a form of cell death caused by excessive oxidation of lipids in the cell membrane.
The researchers tested the effect of FSP1 inhibitors in animal models, using melanoma tumors that had spread to the lymph nodes of mice.
The results showed that blocking FSP1 significantly reduces tumor growth in this environment.
Interestingly, in experiments on melanoma cells grown in the laboratory (in vitro), the same treatment had minor effects, suggesting that the body’s environment plays a decisive role in how cancer defends itself against cell death.
“We observed that melanoma cells in lymph nodes become dependent on FSP1 for survival and that inhibiting it can reduce their proliferation,” lead author Jessalyn Ubellacker, Ph.D., assistant professor of molecular metabolism, explained in a statement.
The team points out that these results can be the basis of new therapeutic strategies aimed at slowing the evolution of cancer by targeting the defense mechanisms against ferroptosis.
Ferroptosis has been researched for several years as an alternative method of destroying cancer cells. However, most previous studies have focused on experiments in laboratory conditions, without analyzing how the real biological environment influences resistance to this process.
In addition, the study highlights that not all tumor cells respond in the same way: the tissue context – that is, the environment of the organ in which they arrive – can determine which antioxidant systems are activated for survival. This specific adaptation explains why metastases, not primary tumors, are responsible for most cancer deaths.
In the same issue of the journal, another study led by researchers from New York University confirmed that inhibiting FSP1 triggers ferroptosis and reduces the growth of lung tumors.
The two studies reinforce the idea that FSP1 represents a promising target for antitumor therapies, regardless of the type of cancer.
The inhibitors used were developed in the laboratories led by Dr. Marcus Conrad (Helmholtz Munich) and Dr. James Olzmann (University of California, Berkeley). Some of the authors of the study are co-founders of the company ROSCUE Therapeutics GmbH, which owns the rights to some of the investigated experimental compounds.
