Cancer: A discovery that could change everything
- David Moreno
- 5 days ago
- 3 min read
Updated: 3 days ago
Iron is a valuable resource for cancer cells: it stimulates their rapid and harmful proliferation in the tissues of the patient. At the Curie Institute, Raphaël Rodriguez and his team are transforming this appetite for iron into a powerful weapon against metastases. Here's how.
Cancer cells crave iron. But in excessive amounts, the metal becomes toxic: it generates free radicals that attack the membranes of metastases. This phenomenon, called oxidative stress, can trigger a dramatic form of cell death: ferroptosis, from "ferro" (iron) and "ptosis" (fall, death).
Rodriguez brilliantly exploits the dual role of iron: a factor in survival and metastatic proliferation on the one hand, and a trigger for ferroptosis in cases of excess on the other. His team's innovations open a promising new avenue for combating cancers resistant to conventional treatments: targeted ferroptosis.
A novel strategy: turning iron against cancer
Iron addiction in the most aggressive cancer cells occurs via a particular protein: CD44. This protein, involved in indirect iron transport and located on the surface of cells, is overexpressed (i.e., present in large quantities) in the case of metastases.
The large number of CD44 proteins allows metastases to import, and then store, large quantities of iron (Fe²⁺) in their lysosomes – sort of digestive compartments responsible for breaking down cellular waste.
This is where Raphaël Rodriguez and his team come in, designing a prodrug (a molecule initially inactive that only reacts when it reaches its target): fentomycin, or fento-1. This prodrug lodges itself in the lysosomes of metastases and reacts with stored iron, producing reactive oxygen species (ROS). These ROS then trigger uncontrolled lipid peroxidation, a direct consequence of significant oxidative stress, leading the metastases to iron deficiency.
To return to the beginning of the article, it is as if fento-1 had the effect of potentiating the activity of Fe²⁺ already abundant within lysosomes, leading to a massive production of oxidative stress lethal to metastases.
Another advantage of fento-1 is its preferential activation, which targets cancer cells. This is made possible by the overexpression of CD44, combined with a high concentration of iron in lysosomes – a configuration specific to metastases.
Impressive preclinical results
In vitro tests performed on biopsies from patients with resistant cancers (such as pancreatic cancer) show effective elimination of metastases. Similarly, tests on animal models have proven highly conclusive.
Researchers are now working to improve fento-1 to increase its stability and reduce its toxicity, before considering a potential phase of clinical trials in humans. While there is still a long way to go, the hope of permanently transforming the fight against cancer is taking a new turn.
This text is the result of an automated translation. The first version of this text (in French) is available at the following address:
Sources :
Le cancer se dope au fer – Le Monde
De nouvelles molécules contre les cancers réfractaires métastatiques – La ligue contre le cancer
Raphaël Rodriguez : le chimiste qui veut vaincre les métastases – Arc Aademie
Un traitement prometteur pour les cancers réfractaires – Medscape
Des molécules d’un genre nouveau pour détruire les cellules cancéreuses du pancréas – Institut Curie
Une nouvelle classe de molécules contre les cellules cancéreuses réfractaires – Onco-hemato
