tbuckley/cabot-search huggingface dataset:
CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model
Authors: Jiyoung Yun, Robert Saddawi-Konefka, Benjamin Goldenson, Riyam Al-Msari, Davide Bernareggi, Jaya L Thangaraj, Shiqi Tang, Sonam H Patel, Sarah M Luna, J Silvio Gutkind, Dan Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Natural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A ( CHMP2A ) as a novel mechanism that mediates tumor intrinsic resistance to NK cell activity. Methods Here, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts. Results We found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4 + T cells, CD8 + T cells. NK cell, as well as fewer myeloid-derived suppressor cells (MDSC). Conclusions Together, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.
Favorable impact of PD1/PD-L1 antagonists on bone remodeling: an exploratory prospective clinical study and ex vivo validation
Authors: Tamara Gassner, Christina Chittilappilly, Theo Pirich, Benjamin Neuditschko, Klaus Hackner, Judith Lind, Osman Aksoy, Uwe Graichen, Sascha Klee, Franz Herzog, Christoph Wiesner, Peter Errhalt, Martin Pecherstorfer, Klaus Podar, Sonia Vallet
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling. Methods An exploratory longitudinal study was conducted to assess s erum markers of bone resorption (C-terminal telopeptide, CTX) and formation (procollagen type I N-terminal propeptide, PINP, and osteocalcin, OCN) before each ICI application (programmed cell death 1 (PD1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor) for 6 months or until disease progression in patients with advanced cancer and no evidence of bone metastases. To validate the in vivo results, we evaluated osteoclast (OC) and osteoblast (OB) differentiation on treatment with ICIs. In addition, their effect on bone remodeling was assessed by immunohistochemistry, confocal microscopy, and proteomics analysis in a dynamic 3D bone model. Results During the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation. Conclusion Our study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.
Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors
Authors: Laurent Mathiot, David Combarel, Justin Cagnat, Julia Delahousse, Kaissa Ouali, Aurelien Marabelle, Yohann Loriot, Santiago Ponce, Stephane Champiat, Sophie Broutin, Francois-Xavier Danlos
Journal: Journal for ImmunoTherapy of Cancer (2024)

Patients with advanced cancer, previously treated with immune checkpoint blockade therapy, may retain residual treatment when undergoing the initial infusion of experimental monotherapy in phase 1 clinical trials. ANV419, an antibody-cytokine fusion protein, combines interleukin-2 (IL-2) with an anti-IL-2 monoclonal antibody, aiming to stimulate the expansion of CD8 T and natural killer lymphocytes while restricting regulatory T lymphocytes. In the recent publication of the phase 1 dose escalation study of ANV419, a notable gap exists in detailed information regarding patients’ prior antitumoral treatments, specifically programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) targeted monoclonal antibodies. Some patients likely retained residual anti-PD-1/PD-L1 monoclonal antibodies, potentially influencing the outcomes of ANV419. In a separate clinical cohort, we retrospectively measured the residual concentration of nivolumab and pembrolizumab, revealing persistent serum concentrations of anti-PD-1/PD-L1 antibodies even months after treatment cessation. This underscores the importance of comprehensively documenting prior immunotherapy details in clinical trials. Such information is crucial for understanding potential interactions that may impact both immunological and clinical effects.
Graphene Quantum Dots Nanoantibiotic‐Sensitized TiO<sub>2−</sub><i><sub>x</sub></i> Heterojunctions for Sonodynamic‐Nanocatalytic Therapy of Multidrug‐Resistant Bacterial Infections
Authors: Ying Qian, Jingming Wang, Xudong Geng, Bingqing Jia, Lei Wang, Yong‐Qiang Li, Bijiang Geng, Weimin Huang
Journal: Advanced Healthcare Materials (2024)

The exploration of sonodynamic therapy (SDT) as a possible replacement for antibiotics by creating reactive oxygen species (ROS) is suggested as a non-drug-resistant theranostic method. However, the low-efficiency ROS generation and complex tumor microenvironment which can deplete ROS and promote tumor growth will cause the compromised antibacterial efficacy of SDT. Herein, through an oxygen vacancy engineering strategy, TiO
Therapeutic Psilocybin's Adverse Effects Mostly Resolved Within 2 Days
Authors: Emily Harris
Journal: JAMA (2024)

Akhila Yerubandi, PharmD; Jennifer E. Thomas, PharmD; N. M. Mahmudul Alam Bhuiya, MPharm; Catherine Harrington, PharmD, PhD; Lorenzo Villa Zapata, PhD; Joshua Caballero, PharmD
Estimated Prevalence of Resident-to-Resident Aggression in Assisted Living
Authors: Karl Pillemer, Jeanne A. Teresi, Mildred Ramirez, Joseph Eimicke, Stephanie Silver, Gabriel Boratgis, Rhoda Meador, Leslie Schultz, Jian Kong, Katja Ocepek-Welikson, E-Shien Chang, Mark S. Lachs
Journal: JAMA Network Open (2024)

Importance Resident-to-resident aggression in assisted living facilities can result in physical and psychological harm, but its prevalence is unknown. Objective To estimate the prevalence of resident-to-resident aggression, including physical, verbal, and sexual, among residents in assisted living facilities. Design, Setting, and Participants This study used cross-sectional, observational data from a clinical trial, in which residents of assisted living facilities were monitored for events over a 1-month period. All residents of 14 large facilities randomly selected from 2 geographic locations (N = 1067), except those receiving hospice care (n = 11), were invited to participate; 93 died or moved prior to enrollment. There were 33 family and resident refusals; 930 residents were enrolled. Data were collected between May 30, 2018, and August 11, 2022. Main Outcomes and Measures The data are from a clinical trial testing the effectiveness of an intervention to reduce resident-to-resident aggression. In addition, the study was designed to assess prevalence using the Time 1 (baseline) data, using a probability sample of facilities to allow for this analysis. Resident-to-resident aggression was identified using a mixed-method, case-finding strategy involving 6 sources: (1) cognitively capable resident reports regarding 22 possible events, (2) direct care staff report, (3) staff member reports collected from event-reporting forms, (4) research assistant observation of events in real time, (5) facility accident or incident reports, and (6) resident records. Results The prevalence of resident-to-resident aggression among the 930 participants (mean [SD] age, 88.0 [7.2] years; 738 women [79.4%]) during the past month was estimated to be 15.2% (141 of 930 residents; 95% CI, 12.1%-18.8%). The most common forms of aggression included verbal (11.2% [104 of 930 residents; 95% CI, 8.8%-14.2%]), physical (41 of 930 residents; 4.4% [95% CI, 3.1%-6.3%]), sexual (0.8% [7 of 930 residents; 95% CI, 0.4%-1.6%]), and other (70 of 930 residents; 7.5% [95% CI, 5.5%-10.2%]). These categories are not mutually exclusive as residents could be involved with more than 1 type of aggressive behavior. Conclusions and Relevance In this cross-sectional, observational prevalence study, resident-to-resident aggression in assisted living facilities was highly prevalent. Verbal aggression was the most common form, and physical aggression also occurred frequently. The effects of resident-to-resident aggression can be both morbid and mortal; therefore, intervention research is needed to prevent it and to treat it when it occurs.
Video- vs Robotic-Assisted Thoracic Surgery—The Race for Resource Utilization
Authors: Ioana Baiu
Journal: JAMA Network Open (2024)

Haley I. Tupper, MD, MS, MPH; Brian L. Lawson, PhD, MS, MA; Patricia Kipnis, PhD; Ashish R. Patel, MD; Simon K. Ashiku, MD; Nareg H. Roubinian, MD, MPH; Laura C. Myers, MD; Vincent X. Liu, MD, MS; Jeffrey B. Velotta, MD
Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip
Authors: Irina Veith, Martin Nurmik, Arianna Mencattini, Isabelle Damei, Christine Lansche, Solenn Brosseau, Giacomo Gropplero, Stéphanie Corgnac, Joanna Filippi, Nicolas Poté, Edouard Guenzi, Anaïs Chassac, Pierre Mordant, Jimena Tosello, Christine Sedlik, Eliane Piaggio, Nicolas Girard, Jacques Camonis, Hamasseh Shirvani, Fathia Mami-Chouaib, Fatima Mechta-Grigoriou, Stéphanie Descroix, Eugenio Martinelli, Gérard Zalcman, Maria Carla Parrini
Journal: Cell Reports Medicine (2024)

There is a compelling need for approaches to predict the efficacy of immunotherapy drugs. Tumor-on-chip technology exploits microfluidics to generate 3D cell co-cultures embedded in hydrogels that recapitulate simplified tumor ecosystems. Here, we present the development and validation of lung tumor-on-chip platforms to quickly and precisely measure ex vivo the effects of immune checkpoint inhibitors on T cell-mediated cancer cell death by exploiting the power of live imaging and advanced image analysis algorithms. The integration of autologous immunosuppressive FAP+ cancer-associated fibroblasts impaired the response to anti-PD-1, indicating that tumors-on-chips are capable of recapitulating stroma-dependent mechanisms of immunotherapy resistance. For a small cohort of non-small cell lung cancer patients, we generated personalized tumors-on-chips with their autologous primary cells isolated from fresh tumor samples, and we measured the responses to anti-PD-1 treatment. These results support the power of tumor-on-chip technology in immuno-oncology research and open a path to future clinical validations.
A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development
Authors: Zhijuan Hu, Liang Yang, Maolei Zhang, Haite Tang, Yile Huang, Yujie Su, Yingzhe Ding, Chong Li, Mengfei Wang, Yunhao Zhou, Qing Zhang, Liman Guo, Yue Wu, Qianqian Wang, Ning Liu, Haoran Kang, Yi Wu, Deyang Yao, Yukun Li, Zifeng Ruan, Hao Wang, Feixiang Bao, Guopan Liu, Junwei Wang, Yaofeng Wang, Wuming Wang, Gang Lu, Dajiang Qin, Duanqing Pei, Wai-Yee Chan, Xingguo Liu
Journal: Cell Metabolism (2024)
Targeting low levels of MIF expression as a potential therapeutic strategy for ALS
Authors: Leenor Alfahel, Thomas Gschwendtberger, Velina Kozareva, Laura Dumas, Rachel Gibbs, Alexander Kertser, Kuti Baruch, Shir Zaccai, Joy Kahn, Nadine Thau-Habermann, Reto Eggenschwiler, Jared Sterneckert, Andreas Hermann, Niveda Sundararaman, Vineet Vaibhav, Jennifer E. Van Eyk, Victor F. Rafuse, Ernest Fraenkel, Tobias Cantz, Susanne Petri, Adrian Israelson
Journal: Cell Reports Medicine (2024)

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neuron (MN) loss. We previously discovered that macrophage migration inhibitory factor (MIF), whose levels are extremely low in spinal MNs, inhibits mutant SOD1 misfolding and toxicity. In this study, we show that a single peripheral injection of adeno-associated virus (AAV) delivering MIF into adult SOD1G37R mice significantly improves their motor function, delays disease progression, and extends survival. Moreover, MIF treatment reduces neuroinflammation and misfolded SOD1 accumulation, rescues MNs, and corrects dysregulated pathways as observed by proteomics and transcriptomics. Furthermore, we reveal low MIF levels in human induced pluripotent stem cell-derived MNs from familial ALS patients with different genetic mutations, as well as in post mortem tissues of sporadic ALS patients. Our findings indicate that peripheral MIF administration may provide a potential therapeutic mechanism for modulating misfolded SOD1 in vivo and disease outcome in ALS patients.
Metabolic liability for weight gain in early adulthood
Authors: Venkatesh L. Murthy, Jonathan D. Mosley, Andrew S. Perry, David R. Jacobs, Kahraman Tanriverdi, Shilin Zhao, Konrad T. Sawicki, Mercedes Carnethon, John T. Wilkins, Matthew Nayor, Saumya Das, E. Dale Abel, Jane E. Freedman, Clary B. Clish, Ravi V. Shah
Journal: Cell Reports Medicine (2024)

While weight gain is associated with a host of chronic illnesses, efforts in obesity have relied on single "snapshots" of body mass index (BMI) to guide genetic and molecular discovery. Here, we study >2,000 young adults with metabolomics and proteomics to identify a metabolic liability to weight gain in early adulthood. Using longitudinal regression and penalized regression, we identify a metabolic signature for weight liability, associated with a 2.6% (2.0%–3.2%, p = 7.5 × 10−19) gain in BMI over ≈20 years per SD higher score, after comprehensive adjustment. Identified molecules specified mechanisms of weight gain, including hunger and appetite regulation, energy expenditure, gut microbial metabolism, and host interaction with external exposure. Integration of longitudinal and concurrent measures in regression with Mendelian randomization highlights the complexity of metabolic regulation of weight gain, suggesting caution in interpretation of epidemiologic or genetic effect estimates traditionally used in metabolic research.
Comprehensive proteogenomic characterization of rare kidney tumors
Authors: Ginny Xiaohe Li, Lijun Chen, Yi Hsiao, Rahul Mannan, Yuping Zhang, Jie Luo, Francesca Petralia, Hanbyul Cho, Noshad Hosseini, Felipe da Veiga Leprevost, Anna Calinawan, Yize Li, Shankara Anand, Aniket Dagar, Yifat Geffen, Chandan Kumar-Sinha, Seema Chugh, Anne Le, Sean Ponce, Shenghao Guo, Cissy Zhang, Michael Schnaubelt, Nataly Naser Al Deen, Feng Chen, Wagma Caravan, Andrew Houston, Alex Hopkins, Chelsea J. Newton, Xiaoming Wang, Daniel A. Polasky, Sarah Haynes, Fengchao Yu, Xiaojun Jing, Siqi Chen, Ana I. Robles, Mehdi Mesri, Mathangi Thiagarajan, Eunkyung An, Gad A. Getz, W. Marston Linehan, Galen Hostetter, Scott D. Jewell, Daniel W. Chan, Pei Wang, Gilbert S. Omenn, Rohit Mehra, Christopher J. Ricketts, Li Ding, Arul M. Chinnaiyan, Marcin P. Cieslik, Saravana M. Dhanasekaran, Hui Zhang, Alexey I. Nesvizhskii, Alexander J. Lazar, Amanda G. Paulovich, Andrzej Antczak, Anthony Green, Avi Ma’ayan, Barb Pruetz, Bing Zhang, Boris Reva, Brian J. Druker, Charles A. Goldthwaite, Chet Birger, D.R. Mani, David Chesla, David Fenyö, Eric E. Schadt, George Wilson, Iga Kołodziejczak, Ivy John, Jason Hafron, Josh Vo, Kakhaber Zaalishvili, Karen A. Ketchum, Karin D. Rodland, Kristen Nyce, Maciej Wiznerowicz, Marcin J. Domagalski, Meenakshi Anurag, Melissa Borucki, Michael A. Gillette, Michael J. Birrer, Nathan J. Edwards, Negin Vatanian, Pamela VanderKolk, Peter B. McGarvey, Rajiv Dhir, Ratna R. Thangudu, Reese Crispen, Richard D. Smith, Samuel H. Payne, Sandra Cottingham, Shuang Cai, Steven A. Carr, Tao Liu, Toan Le, Weiping Ma, Xu Zhang, Yin Lu, Yvonne Shutack, Zhen Zhang
Journal: Cell Reports Medicine (2024)

Non-clear cell renal cell carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis of aggressive disease, and therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses of 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, and metabolic aberrations in RCC subtypes. RCCs with high genome instability display overexpression of IGF2BP3 and PYCR1. Integration of single-cell and bulk transcriptome data predicts diverse cell-of-origin and clarifies RCC subtype-specific proteogenomic signatures. Expression of biomarkers MAPRE3, ADGRF5, and GPNMB differentiates renal oncocytoma from chromophobe RCC, and PIGR and SOSTDC1 distinguish papillary RCC from MTSCC. This study expands our knowledge of proteogenomic signatures, biomarkers, and potential therapeutic targets in non-ccRCC.
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma
Authors: Alessandra De Leo, Alessio Ugolini, Xiaoqing Yu, Fabio Scirocchi, Delia Scocozza, Barbara Peixoto, Angelica Pace, Luca D'Angelo, James K C Liu, Arnold B Etame, Aurelia Rughetti, Marianna Nuti, Antonio Santoro, Michael A Vogelbaum, Jose R Conejo-Garcia, Paulo C Rodriguez, Filippo Veglia
Journal: Immunity (2024)
Use of medical therapy and risk of clinical events according to frailty in heart failure patients – A real‐life cohort study
Authors: Deewa Zahir Anjum, Jarl E. Strange, Emil Fosbøl, Caroline Hartwell Garred, Mariam Elmegaard, Charlotte Andersson, Pardeep S. Jhund, John J.V. McMurray, Mark C. Petrie, Lars Kober, Morten Schou
Journal: European Journal of Heart Failure (2024)
Prostate‐Specific Membrane Antigen Targeted StarPEG Nanocarrier for Imaging and Therapy of Prostate Cancer
Authors: Niranjan Meher, Gary W. Ashley, Kondapa Naidu Bobba, Anju Wadhwa, Anil P. Bidkar, Chandrashekhar Dasari, Changhua Mu, Ramya Ambur Sankaranarayanan, Juan A. Camara Serrano, Athira Raveendran, David P. Bulkley, Rahul Aggarwal, Nancy Y. Greenland, Adam Oskowitz, David M. Wilson, Youngho Seo, Daniel V. Santi, Henry F. VanBrocklin, Robert R. Flavell
Journal: Advanced Healthcare Materials (2024)

The tumor uptake of large non-targeted nanocarriers primarily occurs through passive extravasation, known as the enhanced permeability and retention (EPR) effect. Prior studies demonstrated improved tumor uptake and retention of 4-arm 40 kDa star polyethylene glycol (StarPEG) polymers for cancer imaging by adding prostate-specific membrane antigen (PSMA) targeting small molecule ligands. To test PSMA-targeted delivery and therapeutic efficacy, StarPEG nanodrugs with/without three copies of PSMA-targeting ligands, ACUPA, are designed and synthesized. For single-photon emission computed tomography (SPECT) imaging and therapy, each nanocarrier is labeled with 177Lu using DOTA radiometal chelator. The radiolabeled nanodrugs, [177Lu]PEG-(DOTA)1 and [177Lu]PEG-(DOTA)1(ACUPA)3, are evaluated in vitro and in vivo using PSMA+ PC3-Pip and/or PSMA- PC3-Flu cell lines, subcutaneous xenografts and disseminated metastatic models. The nanocarriers are efficiently radiolabeled with 177Lu with molar activities 10.8-15.8 MBq/nmol. Besides excellent in vitro PSMA binding affinity (kD = 51.7 nM), the targeted nanocarrier, [177Lu]PEG-(DOTA)1(ACUPA)3, demonstrated excellent in vivo SPECT imaging contrast with 21.3% ID/g PC3-Pip tumors uptake at 192 h. Single doses of 18.5 MBq [177Lu]PEG-(DOTA)1(ACUPA)3 showed complete resolution of the PC3-Pip xenografts observed up to 138 days. Along with PSMA-targeted excellent imaging contrast, these results demonstrated high treatment efficacy of [177Lu]PEG-(DOTA)1(ACUPA)3 for prostate cancer, with potential for clinical translation.
Kernel-based testing for single-cell differential analysis
Authors: A. Ozier-Lafontaine, C. Fourneaux, G. Durif, P. Arsenteva, C. Vallot, O. Gandrillon, S. Gonin-Giraud, B. Michel, F. Picard
Journal: Genome biology (2024)

Abstract Single-cell technologies offer insights into molecular feature distributions, but comparing them poses challenges. We propose a kernel-testing framework for non-linear cell-wise distribution comparison, analyzing gene expression and epigenomic modifications. Our method allows feature-wise and global transcriptome/epigenome comparisons, revealing cell population heterogeneities. Using a classifier based on embedding variability, we identify transitions in cell states, overcoming limitations of traditional single-cell analysis. Applied to single-cell ChIP-Seq data, our approach identifies untreated breast cancer cells with an epigenomic profile resembling persister cells. This demonstrates the effectiveness of kernel testing in uncovering subtle population variations that might be missed by other methods.
Identification and outcomes of <scp>KDIGO</scp>‐defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure
Authors: Samir S. Patel, Venkatesh K. Raman, Sijian Zhang, Prakash Deedwania, Qing Zeng‐Treitler, Wen‐Chih Wu, Phillip H. Lam, George Bakris, Hans Moore, Paul A. Heidenreich, Janani Rangaswami, Charity J. Morgan, Yan Cheng, Helen M. Sheriff, Charles Faselis, Ravindra L. Mehta, Stefan D. Anker, Gregg C. Fonarow, Ali Ahmed
Journal: European Journal of Heart Failure (2024)
Ferroptotic therapy in cancer: benefits, side effects, and risks
Authors: Jiandong Diao, Yuanyuan Jia, Enyong Dai, Jiao Liu, Rui Kang, Daolin Tang, Leng Han, Yingjie Zhong, Lingjun Meng
Journal: Molecular Cancer (2024)

Abstract Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various cancer types. However, it can lead to side effects, including immune cell death, bone marrow impairment, liver and kidney damage, cachexia (severe weight loss and muscle wasting), and secondary tumorigenesis. In this review, we discuss the advantages and offer an overview of the diverse range of documented side effects. Furthermore, we examine the underlying mechanisms and explore potential strategies for side effect mitigation.