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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Tuesday, April 23, 2024
Treatment failure and high mortality in non–small cell lung cancer (NSCLC) are often attributed to chemotherapy resistance, and recent studies have identified dysregulation of apoptosis as a key factor. During the American Association for Cancer Research (AACR) Annual Meeting 2024, Akhil Srivastava, PhD, of the University of Missouri School of Medicine, Columbia, and colleagues presented the results from their study, which aimed to evaluate how ferroptosis—a nonapoptotic type of regulated cell death—may serve as an effective treatment option in chemoresistant NSCLC (Abstract LB020/2).
“We report here the synthesis of a novel EV-IONP–based system that can intrinsically induce ferroptosis and overcome chemoresistance by circumventing the conventional apoptosis-based resistance,” concluded the investigators. “Our [findings are] expected to develop a potent cancer treatment strategy for efficiently treating resistant NSCLC tumors.”
The study authors developed a novel extracellular vesicle-iron oxide nanoparticle (IONP) hybrid system (ExoFeR) derived from normal lung fibroblast cells that was able to induce ferroptosis. The ExoFeR complex was characterized by inductively coupled plasma mass spectrometry, transmission electron microscopy, and through Zeta potential measurements. NSCLC A549 cells and patient-derived cisplatin-resistant NSCLC tumoroids were exposed to the system to activate ferroptosis. The induction of ferroptosis was confirmed via various staining methods, as well as the identification of ferroptosis markers GPX4 and SLC7A11/xCT. Patient-derived tumoroids and A549 cells were evaluated for sensitivity to chemotherapeutic agents.
The novel system was determined to be successfully formulated according to physicochemical characterization. Analyses confirmed a reduction in GPX4 and SLC7A11/xCT protein expression levels in ExoFeR-treated patient-derived tumoroids and NSCLC cells, suggesting an induction of ferroptosis. Further evaluation also concluded the sensitization to cisplatin in NSCLC cells and resistant patient-derived tumoroids after ExoFeR treatment.
Disclosure: The study authors reported no conflicts of interest.
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