Cancer: New hope for fighting the most refractory malignant cells
Now a French research team, led by scientists from the Curie Institute, the CNRS and Inserm, has just developed a new class of small molecules capable of causing the destruction of cell membranes and therefore the death of these cells.
This study is based on the properties of so-called persistent cancer cells, with high metastatic potential; they express on their surface a large quantity of a protein called CD44 which allows them to internalize iron, making them more aggressive and able to survive chemotherapy.
But by accumulating iron, they become more vulnerable to a cell death mechanism called ferroptosis. This process, catalyzed by iron, leads to the breakdown of lipids that form the cell's internal membranes.
The researchers capitalized on this weakness to develop a hybrid molecule—fentomycin (Fento-1)—capable of striking the heart of these most resistant cells. Developed by chemist Raphaël Rodriguez's team, it accumulates specifically in lysosomes—the iron-rich cellular compartments of CD44+ cells—thanks to a sequence capable of crossing the plasma membrane and entering the cell via an endocytosis mechanism. It then releases an active fragment that locally intensifies iron reactivity.
Following administration of Fento-1, researchers noted a significant reduction in tumor growth in preclinical models of metastatic breast cancers as well as a pronounced cytotoxic effect on biopsies of pancreatic cancers and sarcomas from patients, confirming the efficacy of the treatment at the preclinical level on these cancers for which the efficacy of conventional chemotherapies is limited.
