A groundbreaking study published in Nature has unveiled a new class of small molecules that have the potential to revolutionize cancer treatment. Developed by a team of researchers from Institut Curie, the CNRS, and Inserm in France, these molecules target drug-tolerant persister cancer cells with high metastatic potential, which are notoriously resistant to traditional cancer therapies.
These cancer cells express a protein called CD44, allowing them to internalize more iron and adapt to standard treatments. The researchers found that these cells are particularly sensitive to ferroptosis, a cell death process catalyzed by iron that causes the oxidation and degradation of membrane lipids.
Through innovative chemistry, the team led by Raphaël Rodriguez demonstrated that iron-induced cell death in lysosomes can disrupt the structure of intracellular membrane compartments. By reacting with hydrogen peroxide, iron generates oxygen-centered radicals that damage cell membranes, ultimately leading to cell death.
Building on these findings, the scientists designed and synthesized a new class of small molecules known as phospholipid degraders, which can activate ferroptosis. These molecules target the cell membrane and accumulate in lysosomes, where they increase the reactivity of iron, triggering ferroptosis in pro-metastatic cancer cells.
One of the key molecules developed, fentomycin (Fento-1), was shown to significantly reduce tumor growth in pre-clinical models of metastatic breast cancer. It also exhibited a potent cytotoxic effect on biopsies from patients with pancreatic cancer and sarcoma, highlighting its potential as a novel treatment approach for these challenging cancers.
The researchers believe that these findings could open up new therapeutic avenues for cancer treatment, especially for cancers that are refractory to standard therapies and have high metastatic potential. Clinical trials are needed to further validate the effectiveness of these molecules in targeting aggressive cancer cells and complementing existing chemotherapy regimens.
This groundbreaking research offers hope for the development of more effective and targeted treatments for aggressive and treatment-resistant cancers, potentially saving countless lives in the future.
