Study finds shutting down one protein makes lung cancer cells self-destruct

Researchers uncovered a powerful weakness in lung cancer by shutting down a protein that helps tumours survive stressWhen this protein FSP1 was blocked lung tumours in mice shrank dramatically with many cancer cells essentially triggering their own selfdestruct mode The work points to a fresh strategy for targeting stubborn lung cancersResearchers at NYU Langone Health have identified how a specific form of cell death linked to the buildup of highly reactive molecules can slow the growth of lung tumoursThis type of cell death known as ferroptosis originally evolved as a way for the body to clear out cells that become overly stressedCancer cells fall into this category yet over time they have developed ways to block ferroptosis so they can continue multiplying even under damaging conditionsA study published online November 5 in Nature showed that an experimental therapy targeting a protein called ferroptosis suppressor protein 1 FSP1 significantly reduced tumour growth in mice with lung adenocarcinoma LUADBlocking this protein which helps cancer cells avoid ferroptosis shrank tumours by as much as 8037Lung cancer remains the worlds leading cause of cancerrelated deaths and LUAD is the most common form among nonsmokers accounting for about 4037 of casesThis first test of a drug that blocks ferroptosis suppression highlights the importance of the process to cancer cell survival and paves the way for a new treatment strategy said senior study author Thales Papagiannakopoulos PhDGW1 an associate professor in the Department of PathologyGW2 at the NYU Grossman School of MedicineReactive Molecules and Their Role in Cell DamageFerroptosis takes place when iron levels rise inside cells fueling the production of highly reactive molecules made from oxygen water and hydrogen peroxide known as reactive oxygen species ROSIn small amounts ROS help cells communicate In excess they create oxidative stress which occurs when ROS add oxygen molecules to vital proteins and DNA damaging or breaking them apart ROS can also harm fats that form the outer membranes of cells contributing to cell death and tissue injuryBlocking FSP1 Shows Strong TumorSuppressing EffectsTo investigate how FSP1 affects lung cancer the research team genetically modified mice so that their lung cancer cells lacked the FSP1 geneThese mice developed smaller tumours due to increased cancer cell death The researchers also tested icFSP1 a newer drug designed to inhibit FSP1Mice treated with icFSP1 lived longer and experienced tumour reductions similar to those seen in mice whose cancer cells were engineered to lack FSP1The study also found that FSP1 may be a more promising treatment target than another ferroptosisblocking protein glutathione peroxidase 4 GPX4 which has been studied in cancer research for a longer periodThe findings suggest that FSP1 is more actively involved in preventing ferroptosis in lung cancer cells while playing a smaller role in normal cell function which could translate to fewer side effectsIncreased levels of FSP1 were also associated with poorer survival rates in human LUAD patients unlike GPX4Future Directions and Ongoing ResearchOur future research will focus on optimising FSP1 inhibitors and investigating the potential of harnessing ferroptosis as a treatment strategy for other solid tumours such as pancreatic cancer said lead study author Katherine Wu an MDPhD student working in the Papagiannakopoulos labWe aim to translate these findings from the lab into novel clinical therapies for cancer patients added author Katherine WuThis story has been sourced from a third party syndicated feed agencies Midday accepts no responsibility or liability for its dependability trustworthiness reliability and data of the text Midday managementmiddaycom reserves the sole right to alter delete or remove without notice the content in its absolute discretion for any reason whatsoever