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3. Raphaël Rodriguez: The French Chemist Challenging Cancer Cells’ Achilles’ Heel

Raphaël Rodriguez, a chemist at the CNRS and Curie Institute, has pinpointed a critical weakness in metastatic cells: an iron overload. His development of fentomycin offers a promising new strategy to destroy these otherwise resilient cells.

At the Curie Institute in the heart of Paris, a low-profile chemist is taking on one of the biggest puzzles in modern cancer research. Raphaël Rodriguez, a research director at the CNRS, has spent years investigating how metastatic cells —scattered, dormant tumor cells that often evade treatment — manage to defy medicine. More importantly, he is focused on how to defeat them. His latest discovery, featured in a study published in Nature in May 2025 (Rodriguez et al., Nature, 2025), offers a response that is both elegant and radical: turning iron against cancer.

The most aggressive metastatic cells — particularly those with high levels of the CD44 protein (i.e., showing high expression of CD44, a protein associated with the most invasive forms of cancer) — share a distinct trait: they store iron in far greater quantities than normal. While this metal fuels their survival and aggressiveness, the overload becomes a liability. Researchers have found that these cells contain a reservoir of free iron that makes them especially vulnerable to a process known as ferroptosis.

 Iron as a Target and a Tool

The concept is straightforward yet powerful. Inside cells, iron reacts with specific oxidants to generate free radicals. This well-known process, known as the Fenton reaction, causes widespread lipid peroxidation—particularly in cell membranes. This biochemical chain reaction culminates in a form of cell death called ferroptosis, literally meaning “death by iron.”

To address this critical flaw, Rodriguez and his team developed a novel molecule: fentomycin 1 (Fento 1). This bifunctional compound has two key properties: it binds to cell membranes and is then taken up into lysosomes, the organelles responsible for cellular recycling. It is within these lysosomes that iron is most active.

Once inside the lysosomes, Fento 1 interacts with iron to produce highly reactive hydroxyl radicals. These radicals attack the lysosomal membrane, causing it to rupture and release enzymes and ferrous ions into the cytoplasm. The cell then undergoes oxidative self-destruction.

The results are striking. In vitro, Fento 1 effectively eliminates CD44^high cells derived from sarcomas and pancreatic cancers. On human biopsies ex vivo, the molecule targets dormant cells that are often resistant to chemotherapy. And in mouse models—particularly for triple-negative breast cancer—injecting Fento 1 directly into lymph nodes leads to a significant reduction in tumor mass, with no major toxic side effects observed (Nature, 2025).

This approach goes beyond introducing a new molecule, it fundamentally changes the treatment strategy. Whereas traditional medicine has focused on genetic mutations or actively dividing cells, this method targets a stable metabolic trait: the intracellular storage of iron. According to Rodriguez, this represents a genuine paradigm shift—the target is no longer just genetic but biochemical. It offers a novel perspective on the vulnerabilities of metastatic cells.

Looking ahead, developments are already underway. Phase I clinical trials are planned to assess the safety of Fento 1 in humans. Variants of the molecule are also being studied to improve its bioavailability. Ultimately, this new class of therapy could target dormant metastases, which account for roughly 70% of cancer deaths, according to the Curie Institute.

Rodriguez, already recognized for his work on free radicals and oxidative stress, continues to follow a consistent intellectual thread: turning the cell’s internal imbalances into therapeutic leverage. He belongs to a generation of researchers who read biological complexity as a language and aim to deliver chemical responses with surgical precision.