Innovative Iron-Activated Molecules Offer Hope Against Resistant and Aggressive Cancer Cells

Recent advances in cancer research have unveiled promising strategies to combat highly aggressive and treatment-resistant cancer cells. A team of scientists from the Institut Curie, collaborating with CNRS and Inserm, has developed a new class of small molecules capable of selectively inducing cancer cell death through ferroptosis—a form of iron-dependent cell death. These molecules are designed to target and disrupt cancer cell membranes, especially those of drug-tolerant persister cells which display high metastatic potential and express elevated levels of the CD44 protein, enabling increased iron uptake and resilience against standard therapies.

Ferroptosis is initiated when iron catalyzes oxidation processes that degrade membrane lipids, leading to cell death. The researchers harnessed this mechanism by engineering molecules that accumulate in lysosomes—cellular compartments rich in iron—and react with hydrogen peroxide to generate reactive radicals. These radicals damage membranes from within, propagating lipid peroxidation across various organelles and ultimately causing cell demise.

The innovative compounds feature a dual-purpose design: one segment targets the plasma membrane, facilitating accumulation in lysosomes through endocytosis, while another enhances iron reactivity within lysosomes to trigger ferroptosis specifically in metastatic cancer cells. Notably, the molecule Fento-1, which is fluorescent, allowed scientists to visualize its localization and activity within cells.

Testing in preclinical models of metastatic breast cancer demonstrated significant tumor reduction following treatment with these molecules. Additionally, biopsies from pancreatic cancer and sarcoma patients showed pronounced cytotoxic effects, highlighting the potential of this approach especially for cancers that are resistant to conventional chemotherapy.

While these findings are promising, clinical trials are essential to establish safety and efficacy in humans. If successful, this strategy could complement existing treatments by targeting pro-metastatic cancer cells that currently evade standard therapies, potentially reducing cancer metastasis and improving patient outcomes.

Source: Medical Xpress