(Press-News.org)
Current anticancer treatments essentially target the primary tumour cells that proliferate quickly, but do not effectively eliminate specific cancer cells able to adapt to existing treatments and which exhibit high metastatic potential1. Yet metastases are responsible for 70% of cancer deaths.
A French research team from Institut Curie, the CNRS and Inserm has just developed a new class of small molecules that bring about the destruction of cell membranes, and hence triggers cell death. Led by scientists at the Laboratory of Biomedicine (Institut Curie/CNRS/Inserm)2, this study is based on the remarkable properties of what are known as drug-tolerant persister cancer cells, with high metastatic potential. The latter express a large quantity of the protein CD44 at their surface, allowing them to internalise more iron, making them more aggressive and able to adapt to standard treatments. These cells are consequently more sensitive to ferroptosis, a cell death process catalysed by iron, which causes oxidation and the degradation of membrane lipids.
Thanks to innovative chemistry developed by the team led by Raphaël Rodriguez, researchers showed that the cell death initiated by iron in lysosomes3 can alter the structure of intracellular membrane compartments. In the lysosomal compartment, iron can react with hydrogen peroxide, generating oxygen-centred radicals, highly-reactive chemical entities that damage cell membranes. This reaction then propagates in the cell forming lipid peroxides in the membranes of other cellular organelles, ultimately causing cell death. Ferroptosis thus results from the cell’s failure to repair the membrane damage.
Using these initial discoveries, the scientists successfully conceived and synthesised a new class of small molecules that can activate ferroptosis: phospholipid degraders. The molecules possess one fragment that allows them to target the cell membrane (plasma membrane)—and to then accumulate in lysosomes via endocytosis—as well as another part that binds to and increases the reactivity of iron, which is abundant in this compartment of pro-metastatic cancer cells, thereby triggering ferroptosis. The molecule fentomycin (Fento-1) was designed to be fluorescent, allowing scientists to visualise it in the cell using high-resolution microscopy, as well as to confirm its localisation in lysosomes.
After the administration of Fento-1, the researchers observed a significant reduction in tumor growth in pre-clinical models for metastatic breast cancer, in addition to a pronounced cytotoxic effect on biopsies of pancreatic cancer and sarcoma patients, thereby confirming the treatment’s effectiveness at the pre-clinical level4 for these cancers, for which the effectiveness of standard chemotherapy is limited.
Clinical tests are needed to show that this ability to induce ferroptosis could serve as a therapeutic avenue that complements current chemotherapy in the fight against cancer, especially by targeting cancer cells that are pro-metastatic and refractory to standard treatments.
This research notably received support from the Ligue contre le cancer (3 Equipe Labellisées), the Horizon 2020 Research and Innovation Programme of the European Union (ERC), the Fondation pour la recherche médicale, the Fondation Charles Defforey–Institut de France, the Klaus Grohe Foundation, l’Institut national du cancer, the Ile-de-France Region, the ANR, the Fondation Bettencourt Schueller, the CNRS, Institut Curie, and Inserm.
1 – Tumour cells that detach from their site of origin and migrate toward other parts of the body, forming new tumours known as metastases. This ability to spread is a characteristic of advanced cancers.
2 – This research primarily involved scientists from the Laboratory of Biomedicine (Institut Curie/CNRS/Inserm/PSL Research University), the Cancer Research Center of Marseille (Aix-Marseille Université/CNRS/Inserm/Institut Paoli Calmette), the APHP (Hôpital Paul-Brousse), the Institute of Molecular Chemistry and Materials of Orsay (CNRS/Université Paris-Saclay), Harvard T.H. Chan School of Public Health, Helmholtz Zentrum München, Julius-Maximilians-Universität Würzburg,, Columbia University and the University of Ottawa.
3 - Lysosomes are the organelles responsible for the degradation of cell debris, biological macromolecules, foreign particles (bacteria, viruses, and parasites), and damaged intracellular organelles.
4 – Pre-clinical tests on animals showed a significant decrease in tumour volume after the lymphatic injection of Fento-1, with tolerance to treatment.
END
A landmark study published by scientists at the University of California San Diego is redefining science’s understanding of the way learning takes place. The findings, published in the journal Nature and supported by the National Institutes of Health and U.S. National Science Foundation, provide novel insights on how brain wiring changes during learning periods, offering a path to new therapies and technologies that aid neurological disorders.
For many years, neuroscientists have isolated the brain’s primary ...
NEW YORK — Our attraction to sugar has grown to an unhealthy level. The average person in the United States now consumes more than 100 pounds of the sweet stuff every year, up from 18 pounds in 1800.
With new research published May 7, in Cell, Columbia University scientists have taken a major step toward dealing with this public health crisis. For the first time, they have mapped the 3-D structure of the human sweet taste receptor, the molecular machine that allows us to taste sweet things. This could lead to the discovery of new regulators of the receptor that would significantly alter our attraction to and appetite for sugar.
"The ...
A landmark study exploring Canadians’ consumption of chips, frozen pizzas, breakfast cereals and other ultra-processed foods typically loaded with fat, sugar and additives has confirmed these foods are directly and significantly linked to poor health outcomes.
Researchers at McMaster University investigated the relationship between ultra-processed food (UPF) consumption and risk factors including blood pressure, cholesterol levels (LDL and HDL), waist circumference and body mass index (BMI).
Their study is the first in Canada to leverage population-based and robust biomarker data to examine this relationship.
The team analyzed data from more than ...
“Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women.”
BUFFALO, NY — May 7, 2025 — A new research paper was published in Aging (Aging-US) Volume 17, Issue 4, on April 4, 2025, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.”
A research team led by first author Mauricio Moel and corresponding author Stefanie L. Morgan from AgelessRx conducted a clinical trial to ...
More than half of Black and Latina women in a study in South Los Angeles reported using personal care products that contain formaldehyde-releasing preservatives. Given that formaldehyde is known to cause cancer in humans, the study reveals both critical safety gaps in how personal care products are regulated in the United States and their disproportionate health impacts on women of color.
In recent years, growing concerns about exposure to formaldehyde in personal care products have focused on hair relaxers. For instance, recent studies show a link between ...
Surgical face masks help prevent the spread of airborne pathogens and therefore were ubiquitous during the COVID-19 pandemic. Now, a modified mask could also protect a wearer by detecting health conditions, including chronic kidney disease. Researchers reporting in ACS Sensors incorporated a specialized breath sensor within the fabric of a face mask to detect metabolites associated with the disease. In initial tests, the sensor correctly identified people with the condition most of the time.
Kidneys remove waste products made by the body’s metabolic processes. But in the ...
ARLINGTON HEIGHTS, Ill. (May 7, 2025) – People who have struggled with asthma or allergies for years understand the psychological toll of these conditions. The May issue of Annals of Allergy, Asthma and Immunology (Annals), the scientific journal of the American College of Allergy, Asthma and Immunology, explores the mental health burden these conditions can exact.
“The diseases we treat in allergy/immunology are primarily chronic illnesses and they often have a psychological impact on those who suffer from them,” says allergist Mitchell Grayson, MD, ...
Learning about one’s risk for Alzheimer’s disease may not lead to emotional distress, but motivation to maintain healthy lifestyle changes tends to fade over time, even in people at high risk, according to a study involving a Rutgers Health researcher.
The study, published in Alzheimer’s & Dementia, was written by Sapir Golan Shekhtman, a doctoral degree student at the Joseph Sagol Neuroscience Center at the Sheba Medical Center in Israel, and led by Orit Lesman-Segev, a neuroradiologist at the Department of Diagnostic Imaging and researcher at the Joseph Sagol Neuroscience Center, Sheba Medical Center ...
Two new advanced predictive algorithms use information about a person’s health conditions and simple blood tests to accurately predict a patient’s chances of having a currently undiagnosed cancer, including hard to diagnose liver and oral cancers. The new models could revolutionise how cancer is detected in primary care, and make it easier for patients to get treatment at much earlier stages.
The NHS currently uses prediction algorithms, such as the QCancer scores, to combine relevant ...
Wealthy individuals have a higher carbon footprint. A new study published in Nature Climate Change quantifies the climate outcomes of these inequalities. It finds that the world’s wealthiest 10% are responsible for two thirds of observed global warming since 1990 and the resulting increases in climate extremes such as heatwaves and droughts.
The study assesses the contribution of the highest emitting groups within societies and finds that the top 1% of the wealthiest individuals globally contributed 26 times the global average to increases in monthly 1-in-100-year heat extremes globally and 17 times more to ...
