Iron & Cancer: Overcoming Resistance with Lysosomal Targeting
- A collaborative research team in France has identified a novel class of molecules, known as fentomycins, capable of eliminating cancer cells that resist conventional treatments.
- These phospholipid degraders induce ferroptosis,a form of cell death triggered by iron.
- Raphaël Rodriguez, research director at CNRS and co-author, explained that cancer cells with metastatic potential often exhibit high levels of the CD44 protein, enabling them to internalize iron.
Groundbreaking research reveals fentomycins,novel molecules,can eliminate drug-resistant cancer cells by triggering ferroptosis,an iron-dependent cell death.This innovative approach offers a potential breakthrough in treating arduous-to-target cancers like pancreatic cancer and sarcomas, where current treatments often fail. Teh fentomycins, designed to target and destroy cancer cell membranes, have shown impressive results in preclinical models, reducing tumor growth, especially when used in combination with existing therapies.Iron and cancer are linked in a way scientists are quickly figuring out how to utilize. News directory 3 reported on how the research team engineered phospholipid degraders to activate ferroptosis. Further studies and clinical trials are underway to evaluate this promising new therapeutic strategy. Discover what’s next for this exciting area of cancer research.
New molecules Target Drug-Resistant Cancer Cells, Inducing Ferroptosis
Updated June 09, 2025
A collaborative research team in France has identified a novel class of molecules, known as fentomycins, capable of eliminating cancer cells that resist conventional treatments. The team, comprised of scientists from the Center national de la recherche scientifique (CNRS), Institut Curie, and Institut national de la santé et de la recherche médicale (Inserm), published their findings in Nature.
These phospholipid degraders induce ferroptosis,a form of cell death triggered by iron. This approach offers a potential new avenue for treating cancers, such as pancreatic cancer and sarcomas, where therapeutic options are limited. Current cancer treatments often fail to eradicate cells with metastatic potential, which are responsible for a large percentage of cancer-related deaths. The new molecules, named fentomycin-1 (Fento-1), were designed to target and destroy cancer cell membranes.
Raphaël Rodriguez, research director at CNRS and co-author, explained that cancer cells with metastatic potential often exhibit high levels of the CD44 protein, enabling them to internalize iron. While this adaptation aids their survival, it also renders them more susceptible to ferroptosis. Iron reacts with hydrogen peroxide within lysosomes, generating oxygen radicals that damage cell membranes and initiate a chain reaction leading to cell death.
“We were the first to link cancer, adaptability, and vulnerability to ferroptosis,” Rodriguez said. ”Cancer cells can adapt, but they don’t have a thousand identities. they have two: One that proliferates and one that spreads. Today, we target proliferation. We also need to target dissemination.”
The researchers engineered phospholipid degraders to activate ferroptosis. These molecules contain a segment that targets the cell membrane, facilitating penetration and accumulation in lysosomes. A second segment enhances iron reactivity within these compartments of pro-metastatic cancer cells, triggering ferroptosis. The molecules were made fluorescent to confirm their lysosomal localization using fluorescence microscopy.
“Ferroptosis results from the cell’s inability to repair membrane damage,” Rodriguez summarized.
Testing on patient-derived cells, tumor organoids, human biopsies, and animal models revealed that fentomycins demonstrated greater efficacy than standard treatments. In preclinical models of metastatic breast cancer, Fento-1 considerably reduced tumor growth and showed strong cytotoxic effects in biopsies of pancreatic cancers and angiosarcomas. The most promising results occurred when combined with existing therapies.
“The most interesting results come when we combine these molecules with current treatments. The response is even better,” Rodriguez emphasized.
What’s next
Toxicity studies and clinical trials are the next steps in evaluating fentomycins. Rodriguez suggests that industry and investors should be interested in developing this new therapeutic strategy for cancer treatment.