Health. Cancer: Iron Used Against Metastatic Cells? This Promising French Study
Chemotherapy works... up to a point: metastases resist it, which significantly reduces the prognosis for cancer patients. But a team of researchers from the Institut Curie has found a promising solution, at the intersection of biology and chemistry.
The work of Raphaël Rodriguez's team at the Curie Institute looks very promising: it should make it possible to treat metastatic cancers, something that treatments are almost incapable of today. Illustration photo by Sipa
While 430,000 new cases of cancer are detected each year in France , advances in recent decades have significantly reduced their mortality. But treatments still come up against metastases, which are the cause of 70% of cancer deaths . These formidable secondary tumors take root, develop, and often spell the death of patients in the more or less short term.
The latest work from the Curie Institute in Paris could be a game changer: the team led by Raphaël Rodriguez, a research director at the CNRS, has published a promising study in Nature , entitled Lysosomal iron activation triggers ferroptosis in cancer . This work is generating immense interest, as it could help destroy metastases, which result from the migration of cancer cells to several organs.
💊 Researchers at Institut Curie, @cnrs.fr and @inserm.fr have developed a prototype drug that destroys refractory cancer cells by degrading their membranes. 🎥 Dr Raphaël Rodriguez tells us more on video ⤵️ ℹ️ Read the scientific publication in Nature: www.nature.com/articles/s41...
A guest on TMC on Thursday, the researcher outlined the development of cancer on the Quotidien program: "There is the primary tumor, these are cells that have genetically mutated and proliferate in an anarchic manner [...]. And there is the dissemination aspect: cells that leave the primary tumor to migrate into the tissues of vital organs, colonize them and develop secondary tumors - metastases," he described. The problem: "Today, drugs know how to eradicate proliferating cells, but are ineffective against disseminating cells, because they proliferate less."
Because, as Le Journal du CNRS points out, the rapid divisions of the cells that cause the primary tumor to grow "induce selection pressure on their own community." As a result, some of them enter "a sort of dormancy, allowing them to escape treatment." But worse still: "This non-proliferative state is associated in some cases with other properties, namely the ability to migrate to other tissues - in short, to metastasize." However, current treatments - especially chemotherapy - are precisely designed to act on proliferation, and are shown to be little or not at all effective on these "disseminated" cells.
This is where Raphaël Rodriguez and his team seem to have made a major discovery: they have developed a molecule capable of killing these cells with high metastatic potential, thanks to an unexpected vector: iron.
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Raphaël Rodriguez's research has shown that metastatic cells " express on their surface a large amount of a protein called CD44 that allows them to internalize iron - which initially gives them greater aggressiveness and an increased ability to adapt to conventional treatments." But these same cells are thus made "more sensitive to ferroptosis - a process of cell death catalyzed by iron," via the destruction of their membrane by oxidation.
Ferroptosis "is a vulnerability of the cell to iron chemistry," the researcher describes. With a high concentration of iron, it "will react with the hydrogen peroxide (oxygenated water) present in it and produce oxygen free radicals" - which will degrade the lipids forming the membrane of all the cell's compartments (nucleus, mitochondria, etc.) and kill it.
From the initial "strength" of these cells, more aggressive thanks to a better capacity to absorb iron, the team has identified a weakness: their self-destruction by ferroptosis by "saturating" them with iron. On this "ridge line," "our objective is clear," explains Raphaël Rodriguez: "Tipping the balance towards [cell] death rather than dissemination."
A molecule that causes metastases to self-destructHis team therefore developed a molecule called fentomycin-1 (or Fento-1), which has a strong affinity for both lipid membranes and iron. A "discovery" at the frontiers of biology and chemistry, which exacerbates the sensitivity of metastatic cells to oxidation... and therefore to their own destruction.
So far, the molecule has been successfully tested on cells from patients with difficult tumors (pancreatic cancer, sarcoma, etc.) and on animals. The goal now is to verify its "in vivo" efficacy through clinical trials - that is, directly in a patient suffering from metastatic cancer - before possible clinical applications.
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