A groundbreaking discovery by French researchers introduces a novel class of molecules that selectively target and destroy cancer cells resistant to conventional treatments, potentially revolutionizing the fight against metastatic cancer.
Key Points at a Glance
- New molecules induce ferroptosis, a form of iron-dependent cell death, in drug-resistant cancer cells.
- These molecules specifically target cells with high metastatic potential, responsible for 70% of cancer deaths.
- The approach exploits the cancer cells’ own iron metabolism to trigger cell membrane degradation.
- Preclinical studies show promising results; clinical trials are anticipated to confirm efficacy.
In a significant stride towards combating metastatic cancer, scientists from Institut Curie, CNRS, and Inserm have developed a new class of molecules that effectively kill cancer cells resistant to standard treatments. These cells, often responsible for cancer recurrence and metastasis, have long posed a challenge due to their ability to evade conventional therapies.
The innovative approach centers on inducing ferroptosis—a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides leading to cell membrane damage. The newly developed molecules, termed phospholipid degraders, are designed to exploit this pathway. They consist of two functional parts: one that targets the cancer cell membrane and another that facilitates the degradation of phospholipids, essential components of the membrane.
Drug-tolerant persister cancer cells, known for their high metastatic potential, exhibit elevated levels of the protein CD44, which increases their iron uptake. This iron accumulation makes them particularly susceptible to ferroptosis. By harnessing this vulnerability, the phospholipid degraders initiate a cascade of reactions within the lysosomes—cellular organelles involved in waste processing. Here, iron reacts with hydrogen peroxide to produce reactive oxygen species, leading to oxidative damage and the breakdown of cell membranes. The resulting lipid peroxides propagate the damage to other cellular structures, culminating in cell death.
This discovery is particularly noteworthy as metastases account for approximately 70% of cancer-related deaths, and current treatments often fail to eliminate the cells responsible for spreading the disease. The ability of these new molecules to selectively target and destroy such cells offers a promising avenue for therapy.
While the findings are based on preclinical studies, the researchers are optimistic about the potential of these molecules in clinical settings. The next steps involve rigorous clinical trials to assess safety and efficacy in humans. If successful, this approach could lead to the development of treatments that not only prevent cancer recurrence but also significantly reduce mortality associated with metastatic disease.
The study, led by Raphaël Rodriguez and his team at the Laboratory of Biomedicine, represents a collaborative effort to address one of the most pressing challenges in oncology. By turning the cancer cells’ own iron metabolism against them, this strategy exemplifies a novel and targeted approach to cancer therapy.
Source: CNRS
