Unveiling the therapeutic potential of ferroptosis in lung cancer: a comprehensive bibliometric analysis and future therapeutic insights

Abstract

Background

Lung cancer remains the leading cause of cancer-related deaths worldwide, with increasing attention being given to novel therapeutic strategies that target the mechanisms underlying tumor growth and drug resistance. Among these, ferroptosis, a regulated cell death driven by iron-dependent lipid peroxidation, has become a key focus in cancer research. Despite extensive research, the exact role of ferroptosis in lung cancer progression and treatment remains unclear, especially regarding its interaction with immune cells and the tumor microenvironment.

Objective and methods

To address these limitations, this study utilizes a comprehensive bibliometric analysis to explore the current landscape of ferroptosis research in lung cancer. We collected data from the Web of Science Core Collection, covering articles published between 2015 and 2025, and analyzed them using advanced tools such as VOSviewer and CiteSpace.

Results

This study uses a comprehensive bibliometric analysis to uncover key trends and emerging areas related to lung cancer in ferroptosis research. Recently, the focus has shifted from basic mechanisms to clinical applications, particularly in developing GPX4-targeted therapies and combination treatments. With increasing international collaboration, the United States and China have become key players. Interdisciplinary research, especially on ferroptosis and the cancer-immune system, offers new insights into its role in the tumor microenvironment and immunotherapy. Ferroptosis shows excellent promise in overcoming drug resistance by regulating iron-dependent lipid peroxidation and enhancing treatment efficacy. Future research should focus on ferroptosis’ clinical translation, particularly in personalized medicine and overcoming resistance, offering broad prospects for lung cancer treatment.

Conclusion

This paper provides valuable insights into the trends, key contributors, and emerging frontiers of ferroptosis research in lung cancer. It identifies important developments that can serve as a foundation for translating ferroptosis-based therapies into clinical practice, particularly to address drug resistance in lung cancer.

Introduction

According to the latest estimates from the International Agency for Research on Cancer (IARC) in 2022, approximately 2.5 million new cases of lung cancer were diagnosed globally, with over 1.8 million deaths attributed to the disease [1, 2]. Lung cancer remains the most commonly diagnosed cancer type and the leading cause of cancer mortality worldwide, accounting for 18.7% of all cancer-related deaths [2]. Globally, there are significant regional disparities in lung cancer incidence and mortality. Asia accounts for 63.1% of new lung cancer cases, followed by Europe (19.5%) and North America (10.4%). Similarly, in terms of mortality, Asia represents 62.9% of global lung cancer deaths, Europe accounts for 20.7%, and North America for 8.3% [3]. These disparities may reflect variations in smoking prevalence, air pollution levels, and access to healthcare resources across regions [3]. Smoking, as the primary risk factor, has prompted global anti-smoking campaigns, which have played a crucial role in reducing mortality [4]. Additionally, the advent of low-dose computed tomography (CT) screening has improved early detection and treatment outcomes, leading to decreased lung cancer mortality in certain regions [5]. Despite advancements in early detection and treatment, lung cancer continues to be a significant challenge due to the development of resistance to conventional therapies, especially in advanced non-small cell lung cancer (NSCLC). To combat this, novel therapeutic approaches targeting tumor biology and drug resistance mechanisms are essential.

Ferroptosis, a novel form of programmed cell death driven by iron-dependent lipid peroxidation, involves critical molecules and pathways beyond GPX4, including iron metabolism regulators such as transferrin, ferritin, and ferroportin, which maintain intracellular iron metabolism. Lipid peroxidation regulators like long-chain acyl-CoA synthetase 4 (ACSL4) and Lysophosphatidylcholine Acyltransferase 3 (LPCAT3) are also essential in the synthesis of oxidizable phospholipids, further amplifying ferroptosis by promoting the incorporation of polyunsaturated fatty acids into membrane lipids, increasing susceptibility to oxidative damage [6, 7]. Experimental evidence supports its pivotal role in cancer biology. Dixon et al. (2012) first demonstrated that ferroptosis is initiated by intracellular iron accumulation and lipid peroxidation [8], providing a foundation for subsequent research. Building on this, Yang et al. (2014) identified GPX4 as a key regulator of ferroptosis [9], where its inhibition led to selective cancer cell death in preclinical models. These findings highlight the therapeutic potential of targeting ferroptosis in lung cancer, particularly in overcoming drug resistance. Recent studies have further emphasized this potential, with preclinical findings showing that targeting GPX4 can sensitize tumor cells to existing treatments. Emerging drugs, such as FINO2 (a lipid peroxidation amplifier) and iron chelators like deferoxamine, are under investigation for selectively inducing ferroptosis in cancer cells [10]. Ongoing clinical trials are exploring the combination of ferroptosis inducers with immune checkpoint inhibitors, aiming to enhance tumor immunogenicity and improve therapeutic responses in personalized medicine [11]. It has been shown that dysregulated iron metabolism in lung cancer cells leads to the accumulation of iron, which promotes oxidative stress and lipid peroxidation, ultimately triggering ferroptosis [12].

In preclinical models, targeting ferroptosis has shown promising results in sensitizing lung cancer cells to chemotherapy and targeted therapies. GPX4, a key regulator of ferroptosis, has been identified as a potential therapeutic target. Inhibition of GPX4 in lung cancer cells leads to ferroptosis, enhancing the efficacy of existing treatments and overcoming drug resistance [13]. Studies that have linked ferroptosis to metabolic dysregulation in tumor cells, an immunosuppressive milieu, and drug resistance have made ferroptosis a significant focus of lung cancer research. Since the regulation of iron is closely related to the pathways that cause lung cancer [14], it is important to consider the role it plays in the initiation and advancement of tumors, especially in these areas. It has been demonstrated that both iron overload and deficiency affect tumor growth and metastasis, which implies that targeting iron metabolism might offer novel therapeutic approaches to treat lung cancer [15, 16].

The interaction between ferroptosis and immune cells within the tumor microenvironment has garnered considerable attention. Research indicates that macrophages in this environment can promote tumor growth by regulating iron acquisition and release [17, 18]. This iron-mediated interaction might affect not only the survival of the tumor cells but also impair the function of immune cells, thus contributing to immune evasion [18]. Understanding ferroptosis, especially about the immune microenvironment, is key for new therapeutic strategy development [19, 20]. This interaction could enhance the efficacy of immunotherapy, a rapidly growing area in lung cancer treatment. Thus, combining ferroptosis inducers with immune checkpoint inhibitors might represent a novel therapeutic approach to improve patient outcomes.

With the growing research on ferroptosis and lung cancer, bibliometric analysis has emerged as one of the most essential means of reviewing the dynamics and trends in this field. Ferroptosis, a new form of cell death, has become the focus of wide attention due to its involvement in the pathogenesis of lung cancer and its potential use in therapy [21]. The literature seems to be growing in number, enough to show an increase in academic interest regarding the relationship between ferroptosis and lung cancer [21, 22]. Bibliometric analysis will enable academics to grasp such trends, find the critical institutions and contributors, and search for collaboration opportunities [23, 24]. The approach will enable an overall landscape of the current status and future directions that research on ferroptosis and lung cancer may take, allowing an important insight into clinical practice and policy-making.

Methods

Data sources and search strategy

This bibliometric analysis is based on data from the Web of Science Core Collection, PubMed, and Scopus, well-recognized as multidisciplinary citation databases adopted in most bibliometric research. The search was carried out until January 2025, considering all studies on ferroptosis from their inception to the time of data collection. No time limitations were considered, and any form of publication that showed pertinence was included to make the present study broad and complete. Search terms were utilized to ensure comprehensiveness and accuracy: 'ferroptosis' and 'lung cancer' with their related synonyms, such as 'oxytosis' and 'lung neoplasm. The specific search strategy was as follows:

#1 (TS=(Ferroptosis) ) OR TS=(Oxytosis).

#2 (((((((((((((((((TS=(Lung Neoplasms) ) OR TS=(Neoplasms, Pulmonary)) OR TS=(Neoplasm, Pulmonary) ) OR TS= (Pulmonary Neoplasm) ) OR TS=(Pulmonary Neoplasms)) OR TS=(Neoplasms, Lung)) OR TS=(Lung Neoplasm)) OR TS=(Neoplasm, Lung)) OR TS=(Lung Cancer)) OR TS=(Cancer, Lung)) OR TS=(Cancers, Lung)) OR TS=(Lung Cancers)) OR TS=(Cancer of Lung)) OR TS=(Pulmonary Cancer)) OR TS=(Cancer, Pulmonary)) OR TS=(Cancers, Pulmonary)) OR TS=(Pulmonary Cancers)) OR TS=(Cancer of the Lung)

Data selection

A strict inclusion criterion was utilized following the initial search to ensure the relevance and high quality of the chosen literature. Confidentiality of the papers was eliminated when they were only included in the original research publications and review articles; conference abstracts, book chapters, and non-peer-reviewed materials were not included. Furthermore, only publications written in English were kept, and papers that had little bearing on lung cancer or ferroptosis were eliminated to preserve the data's accuracy and specificity.

Tools for data analysis

To support detailed data analysis and visualization, two widely-used bibliometric tools, VOSviewer and CiteSpace, were employed. VOSviewer was utilized to map collaboration networks among authors, institutions, and countries engaged in copper and cancer research, facilitating the identification of key contributors and research groups. It was also applied for keyword co-occurrence analysis, revealing research hotspots. CiteSpace was used for citation network analysis of highly cited and pioneering studies, uncovering developmental trends and key breakthroughs in the field. Additionally, CiteSpace helped identify emerging terms, providing insight into new concepts and methodologies shaping future research directions.

Data visualization

The analysis results were clearly presented through various visual representations generated using VOSviewer and CiteSpace. These included line charts for publication trends, keyword co-occurrence networks, collaboration networks, and co-citation maps, all of which help illustrate the research structure, dynamic developments, and knowledge networks in ferroptosis and lung cancer research.

Research hotspot and trend analysis

The bibliometric research identified a number of major themes and research frontiers in ferroptosis, especially regarding lung cancer. According to the results, ferroptosis has become a significant area of focus for treating lung cancer because of the new type of controlled cell death. It has some potential in explaining molecular pathways and addressing drug resistance. As the field of study develops, ferroptosis will probably be a major factor in the development of therapeutic applications in the future.

Results

A total of 1664 articles were retrieved. Considering that no time limitations were imposed and all relevant publications were included to make the study broad and complete, the final dataset consisted of 1664 research articles.

Figure 1 illustrates the publication trends on ferroptosis genes in the context of lung cancer from 2015 to 2025, including their proportion relative to the total output in the field. Between 2015 and 2018, the publication rate remained modest, with fewer than 15 articles per year. However, by 2019, this number had risen to 33, followed by an exponential increase, peaking at 591 articles by 2024. These data indicate that the importance of ferroptosis in lung cancer research is gradually being recognized, and its potential value in lung cancer treatment is gradually being discovered. In addition, such a rapidly growing number of publications also means more possibilities for international exchanges and cooperation.

Fig. 1.

Trends in Publications on Ferroptosis Genes and Lung Cancer (2015–2025)

Figure 2 highlights influential authors in the field, such as 'Zhan, Cheng' and 'Tao, Yongguang' whose prominent nodes represent their significant contributions. Moreover, authors like 'Wang, Xiang' and 'Bi, Guoshu' act as key collaborative hubs, playing crucial roles in linking various research groups. This highlights the distinct clustering of collaborations in the field. For example, the blue cluster is centred on 'Ma, Lifang' and 'Zhang, Xiao' while the green cluster is anchored by 'Tao, Yongguang', reflecting strong cooperation within these groups. The temporal analysis of the collaborative network highlights evolving partnership trends, with colour gradients ranging from blue (2021) to yellow (2023), indicating the progression of collaborations over time. Prominent authors such as 'Wang, Xiang' and 'Zhan, Cheng' have maintained consistent activity throughout this period, reflecting their sustained influence and strong collaborative networks. At the same time, new contributors like 'Chen, Xiao' and 'Zhang, Jing' have gained prominence in recent years, suggesting they are shaping emerging research directions and facilitating novel collaborations.

Fig. 2.

Comprehensive Mapping of Ferroptosis Research in Lung Cancer. a Research Trends and Key Themes in Ferroptosis: A Bibliometric Overview; b Collaborative Networks in Ferroptosis Research: Global Contributions and Key Institutions; c Emerging Frontiers: Clinical Applications and Future Directions of Ferroptosis in Lung Cancer Treatment

The reference network plot is another way that it shows which publications are connected by the articles; this is because of how many of the publications are in the field of each one, as shown above in the figure of the number of citations, the colour of which is the effect of all of the papers, Key paper such as Li [25] and Bersuker [26] are of high citation, which is an excellent contribution of the paper in the area of each paper.

As depicted in Fig. 3, in terms of the global scientific cooperation network, different clustering and stratification patterns are revealed in the international scientific collaboration network. Especially the US is the central hub of international scientific cooperation, and China and the United States are the dominant countries in international research cooperation. The United States follows the same extensive network with the most significant node, which is the biggest point of China's international cooperation. Countries like the United Kingdom, Australia, and Japan also have important positions in the cooperation network besides these two leaders. The network diagram shows different colours, which are different cooperation clusters. For instance, the cooperation of European countries such as the United States and Sweden shows that there are strong intra-regional collaborations between China, the US, and India, and the two countries have regional cooperation groups.

Fig. 3.

Global Collaboration and Research Dynamics in Ferroptosis and Lung Cancer. a Mapping Global Research Collaborations in Ferroptosis: Key Countries and Institutions; b Identifying Research Clusters and Thematic Focus Areas in Ferroptosis Studies; c Evolution of Research Trends: A Temporal Analysis of Key Contributors and Collaborative Networks

From the temporal point of view, leading nations, including China, the US, and Japan, have continuously maintained high degrees of research cooperation between 2021 and 2024, further strengthening their position as the world's scientific community. Meanwhile, in recent years, developing countries such as India and the United Arab Emirates have intensified international cooperation, gradually increasing their influence in the international research environment. Some partnerships, including those between Germany and Italy, as well as between China and Singapore, have shown relative stability; however, the global collaboration network is still changing. This shows that these countries have long-lasting cooperative tendencies consistent with sustained collaboration and mutual scientific engagement.

Figure 4a presents a detailed analysis of the performance of various research institutions by publication volume, linkage strength, and citation counts. To make the data more distinct for clarity, publication counts and linkage strengths were uniformly scaled up by a factor of 10, and citation frequencies were scaled down by the same factor. The analysis results show that institutions like Fudan University, Central South University, and Shanghai Jiao Tong University are at the forefront of research output and play a dominant role in academic production. Notably, Fudan University and Shanghai Jiao Tong University demonstrate high output and muscular linkage strength, realizing broad domestic and international collaboration. Along with such intense collaboration and high-quality research, these institutions have carved a name for themselves in national and international academic circles.

Fig. 4.

Institutional Influence and Collaborative Network Quantification in Ferroptosis Research. a The Institutional Influencing on the Effect of Ferroptosis Research (Publications and Link strength were enlarged to 10 times their original size, while Citations were reduced to 10% of their original size.); b Global and regional collaboration networks mapping of research clusters in the field of ferroptosis studies; c Citation networks and knowledge flow: tracing the intellectual foundations of ferroptosis research; d Citation flow and knowledge transfer: analysis of the intellectual structure of ferroptosis

Figure 4b and c visualize academic collaboration networks; node size corresponds to the level of collaboration activity, while connected lines draw the strength of partnerships. Different colours illustrate collaborative clusters. Fudan University and Central South University represent the most prominent nodes, which are central to domestic and international networks. This testifies to the high production output of these universities and prominent collaboration efforts. Very closely connected institutions in this category include Zhejiang University and Central South University. The collaborations are powerful at the regional level, where Central South University creates many cross-regional links based on prior relations both domestically and internationally. Furthermore, the figures highlight significant international collaborations, including key partnerships between Shanghai Jiao Tong University, Zhejiang University, and leading research centres in the United States and Europe, emphasizing their research's global scope and impact.

Figure 4d maps citation and collaboration patterns between disciplines, with strong interlinks between all fields. Most impressively, there stands a close interaction between Molecular Biology, Immunology, and Genetics in front of high rates of cross-citation that point to the interdependence of the research findings or breakthroughs in experimental techniques possibly achieved in collaboration. Take, for instance, areas such as gene editing and immunotherapy; most of their progress was pegged on interdisciplinary knowledge and integration, hence the prominence of this interaction. For instance, recent increased collaboration between Systems Computing, Physics, Materials Science, and Chemistry underlines the important role that computational and material sciences are playing in discovering and designing new materials. The increase in such interdisciplinary partnerships accelerates the pace of progress in frontier sciences through new ways of attacking complex challenges. Environmental sciences, such as Ecology, Earth Science, and Marine Science, are increasingly interdisciplinary, sometimes combined with other disciplines in addressing several grand global challenges where collaboration across disciplines is imperative, like climate change and sustainable development.

Figure 5a describes the number of publications and frequencies of citations in different journals, with blue bars for the number of publications and green bars for citing frequencies. This helps to establish a comparison of academic output and its impact. The highest current rates of 64 and 48 publications exist for Frontiers in Oncology and Frontiers in Pharmacology, respectively, pointing out the leadership of these journals within the nets of pharmacology and oncology. Using the same principle, journals of relatively small outputs, such as Signal Transduction and Targeted Therapy, with only 19 published articles, obtained an impressive 2,141 citations, presumably reflecting very high-quality research. In comparison, Cell Death & Disease had 32 articles published and received a total of 874 citations, thus demonstrating its overall importance to the field of cell death and disease research. These comparisons also reveal that academic impact depends not only on how many pieces one publishes but also on the quality of the research one produces, which is important in establishing scholarly influence.

Fig. 5.

Analyzing Research Output and Citation Impact in Ferroptosis. a Journal Contributions to Ferroptosis Research: Publication Output and Citation Frequency; b Keyword Co-Occurrence Network: Mapping Research Themes in Ferroptosis; c Co-Authorship Network Analysis: Identifying Key Collaborators in Ferroptosis Studies

Figure 5b emphasizes the collaboration and citation networks of journals with each other, allowing the mapping of their interdependence and standing within the general research ecology. In this visualization, node size shows the centrality of the journal, lines reflect citation links, and the colour is used to highlight collaborative clusters. For example, large nodes for such journals as Frontiers in Oncology and Frontiers in Pharmacology may indicate that these journals are central in their fields by being well-connected by citations and collaborations. Similarly, the prominent positions of Cell Death & Disease and Chemico-Biological Interactions indicate their academic importance. The figure also shows clear research clusters, with the collaboration between the red and green groups being intensive and citations exchanged frequently. An example would be that the close collaborating network is formed by Frontiers in Genetics, Cancer Research and Frontiers in Pharmacology on genetics, cancer research and pharmacology. These networks realize that scientific advancement depends more on cross-disciplinary liaisons and mutual citations nowadays, especially in areas like pharmacology and research into genetics.

Temporally, Fig. 5c adds a new dimension by giving a perspective on the evolution of journal citation networks over time. The colour gradient of the nodes is from dark blue to yellow, showing different citation activities in different periods. Blue nodes, such as Frontiers in Pharmacology and Frontiers in Oncology, manifest the increase in publication and citation frequencies from 2022 to 2024, indicating that these journals are currently at the frontier of academic research when considering the number of influential articles they publish. On the contrary, the green nodes are really high-impact journals in previous years that still have a strong academic influence, such as Free Radical Biology & Medicine and Cell Death & Disease, meaning this research has sustained value. The figure also reveals emerging research trends and increasing cross-disciplinary collaborations. For example, the expanding citation network of Signal Transduction and Targeted Therapy underscores the rising prominence of signal transduction and targeted therapy as leading fields driven by advances in interdisciplinary research.

Figure 6 illustrates research hotspots, keyword co-occurrences, and the temporal evolution of trends in ferroptosis research. In Fig. 6a, the keyword co-occurrence network highlights 'Ferroptosis' as the central term, closely linked to terms like 'cancer,' 'cell death,' and 'apoptosis,' emphasizing its significance in cancer and cell death studies. The primary research areas focus on cancer treatment and drug resistance, as seen in the frequent appearance of keywords such as 'lung cancer,' 'chemotherapy,' and 'drug resistance.' Additionally, molecular mechanisms like 'autophagy' and 'lipid peroxidation' reflect the deep exploration of ferroptosis at a molecular level. Cross-disciplinary terms such as 'stem cells' and 'nanoparticles' further demonstrate ferroptosis' broader applications, particularly its potential in cancer therapy.

Fig. 6.

Ferroptosis-Related Research Themes Clustering and Temporal Evolution. a Keyword Co-occurrence mapping: to identify core research topics in Ferroptosis; b Temporal evolution of research focus: tracking the shift in focus in studies relating to ferroptosis; c Citation bursts and trending frontier detection: identification of emerging frontiers in Ferroptosis research

Figure 6b describes the time sequence development of research hotspots, in which 'cuproptosis' and 'immunity' are newer keywords, indicating that new forms of cell death and immunotherapies are occupying centre stage with time. This trend is further elaborated in Fig. 6c, showing the thematic evolution of ferroptosis research from 2015 to 2024: 'cuproptosis' and 'bioinformatics analysis' have become the hotspots of this domain, representing the rapid development of this area. Meanwhile, oncology themes like 'cancer sensitivity' and 'cell death' continue to hold priority interest, which is evidence that interest in ferroptosis has been stable since its discovery. Simultaneously, new research areas, including 'oxidative stress' and 'programmed cell death', are gaining much more attention.

As illustrated in Fig. 7, the interest sparked in 2015 made 'cancer cells' one of the important research issues between 2015 and 2020 with a burst strength of 3.46, reflecting their central role in tumor biology, cancer progression, and therapeutic targeting. Similarly, 'messenger RNA' (mRNA), with a burst strength of 1. 93 from 2015 to 2019, gained attention due to its pivotal role in gene expression regulation and vaccine development, especially for mRNA vaccines like COVID-19. 'Gene expression' also maintained a strong burst (3. 29) from 2015 to 2020, emphasizing its relevance in understanding gene regulation and its impact on tumor biology. In 2016, 'sensitivity' had a burst strength of 3. 47, lasting until 2020, reflecting its importance in personalized medicine, particularly in predicting therapeutic responses in cancer treatment. Drug sensitivity assessments help optimize personalized treatment plans, enhancing efficacy while minimizing side effects.

Fig. 7.

Top 25 Keywords with the Strongest Citation Bursts in Ferroptosis Research (2015–2024)

In 2017, several pivotal research topics gained prominence. 'DNA methylation,' with a burst strength of 1. 38 (lasting until 2021), underscored its key role in epigenetics, particularly in regulating tumorigenesis. Around the same time, 'ferroptosis' (1. 34 burst from 2017 to 2019) attracted attention as a novel form of programmed cell death, especially relevant to cancer and neurodegenerative diseases. Short-term bursts for 'breast cancer' (1. 26) and 'cancer stem cells' (1. 25) from 2017 to 2018 indicated a growing focus on breast cancer biology and the role of cancer stem cells in tumor recurrence, drug resistance, and metastasis. From 2018 to 2020, research interest expanded to cell death mechanisms like apoptosis, necrosis, and autophagy, as reflected by the burst strength of 1. 76 for 'death,' particularly in cancer and other diseases. In 2019, research into oxidative stress and anticancer mechanisms intensified. 'Reactive oxygen species' (ROS) had a burst strength of 2. 11 from 2019 to 2020, reflecting its crucial role in cellular damage, cancer development, and antioxidant therapy. During the same period, 'GPX4', with a burst strength of 1. 98, emerged as a key antioxidant enzyme, particularly in the context of ferroptosis. Oxidative stress became a focal point of research, with a burst strength of 1. 55, highlighting its relevance in cancer, aging, and neurodegenerative diseases. Additionally, research into 'anticancer therapy' (1. 44) and 'molecular mechanisms' (1. 39) from 2019 to 2021 underscored continued interest in anticancer drug development and the study of tumor molecular pathways.

In 2020, 'regulator' became a prominent keyword with a burst strength of 2. 53, continuing through 2021, reflecting the growing interest in the role of regulators in signalling pathways, particularly in cancer signal regulation. By 2021, research hotspots like 'lung adenocarcinoma' (2. 16 burst strength from 2021 to 2022) and 'glucose metabolism' (1. 23 burst strength) highlighted the increased focus on the molecular mechanisms and therapeutic strategies for lung cancer and the role of glucose metabolism in tumor growth and survival. From 2022 onward, several keywords entered their burst periods, a trend expected to continue through 2024. 'Migration' (2. 4 burst strength) underscored its critical role in cancer metastasis, while 'lung squamous cell carcinoma' and 'breast' (each with a burst strength of 1. 57) indicated an ongoing interest in cancer subtypes. The 'immune microenvironment' (1. 12 burst strength) pointed to the growing importance of tumor immune environments, particularly in developing novel immunotherapies. Additionally, 'biomarker' and 'artemisinin' (with burst strengths of 1. 12 and 1. 11, respectively) highlighted the crucial role of biomarkers in cancer diagnosis and prognosis and the emerging potential of artemisinin as an anti-cancer agent.

Figure 8 presents a thematic clustering analysis of ferroptosis research related to lung cancer conducted between 2015 and 2024, which has identified 11 major research themes. These themes are visually represented by coloured nodes and links, illustrating the relationships and clustering of key concepts. This analysis provides valuable insights into the evolving focus areas within ferroptosis research.

Fig. 8.

Cluster analysis of lung cancer and ferroptosis research themes

The largest cluster, #0 'Lung Adenocarcinoma', emphasizes the application of ferroptosis in treating lung adenocarcinoma, primarily focusing on regulating ferroptosis to control cancer cell growth, metastasis, and resistance. Closely related, Cluster #1, 'Drug Resistance', reflects the increasing interest in using ferroptosis to overcome resistance to cancer therapies. Cluster #2, 'Combination Therapy', builds on this, exploring how ferroptosis can be integrated with chemotherapy, targeted therapy, or immunotherapy to enhance therapeutic efficacy. On the mechanistic side, Cluster #3 'Mechanisms' delves into the molecular pathways underlying ferroptosis, particularly its role in cellular metabolism and oxidative stress, further deepening our understanding of its biological processes.

Cluster #3, 'Lipid peroxidation', Highlights the crucial part of ferroptosis that lipid peroxidation controls because it is important to control cell death. Additionally, the 'Classification of Cancer Cells' depicted ferroptosis as a therapeutic strategy against the growth and proliferation of tumor cells. The rapidly increasing interest in the use of bioinformatics technology to study signalling pathways, protein interactions, and gene expression and the identification of novel therapeutic targets running parallel, as depicted by Cluster#6, 'Bioinformatics Analysis,' depicts the increasing dependence on bioinformatic tools for this purpose. The application of ferroptosis as a novel method of cancer therapy is the main focus of antitumor therapy, which focuses on the use of this mechanism, which could greatly increase the therapeutic effect of the disease. On the other hand, the term 'ferroptosis' of Cluster#8 illustrates the development of ferroptosis, which is a unique area of investigation, especially for treating cancer resistance resistant to the standard of therapy.

Finally, with a view that ferroptosis mechanism is used by investigators to incorporate ferroptosis pathway into treatment procedures to increase patient outcome, Cluster#9 'Survival' explores the effect of ferroptosis on cancer survival rates; clusters#10 'Lung Cancer' and#11 'Sensitivity' which is used to increase the sensitivity of the drug to lung cancer, and the use of ferroptosis to the cancer of lung cancer; by causing ferroptosis investigators to try and increase the response of cancer cells to therapies; and finally to improve the outcome of lung cancer patients, and ferroptosis in lung cancer is the central theme of ferroptosis research in lung adenocarcinoma; cancer type, drug resistance, combined therapy and molecular mechanism are the main topics for ferroptotic research in the field of lung cancer; the main focus is still on the use of ferroptosis to overcome drug resistance and incorporate ferroptosis into antitumor therapies; and finally to the integrated drug of ferroptosis in the cancer of lung adenocarcinoma; and finally, the combination of ferroptosis with the drug of the cancer can be used in the tumor of lung cancer patients to achieve the best results in this regard.

Ferroptosis is being studied for lung cancer overall, which is concerned with the many different types of cancer, including drug resistance, combination therapy, and molecular mechanisms. Ferroptosis and its application in anticancer treatments are the main focus areas for overcoming drug resistance.

Figure 9 provides a co-citation analysis of ferroptosis research from 2015 to 2025, highlighting key publications and their impact on the field. As shown in the figure, Dixon et al. [8], and Stockwell et al. [27] are the most frequently cited articles, reflecting their central importance. Dixon et al. [8] introduced the fundamental characteristics of ferroptosis, establishing the foundation for future research. Building on this, Stockwell et al. [27] deepened the understanding of ferroptosis mechanisms, particularly its potential in cancer therapy, focusing on overcoming tumor resistance. Other pivotal works, including Bersuker et al. [26], Doll et al. [28], and Jiang et al. [29], have further elucidated ferroptosis mechanisms and explored their clinical applications.

Fig. 9.

The heatmap analysis, co-refire network, and in-measure the significant contributions of Ferroptosis-based. a Co-Occurrence Network of influential references in Ferroptosis Research; b Density Visualization of High-Impact Topics in Ferroptosis Studies

The co-citation clusters illustrate the breadth of research within the field of ferroptosis. The red cluster centres on fundamental mechanistic studies, while the green and blue clusters focus on the relationship between ferroptosis and cancer, particularly regarding cell proliferation, apoptosis, and resistance. A heat map further emphasizes the significant influence of Dixon et al. [8], and Stockwell et al. [27], as these frequently cited works form the foundation of ferroptosis research. Current research hotspots include the molecular mechanisms of ferroptosis, especially the regulation of GPX4 and lipid peroxidation, along with its promising role in overcoming drug resistance in cancer therapy.

As illustrated in Fig. 10, Dixon [8] (Cell) was the first to define ferroptosis as a novel form of regulated cell death, detailing its mechanisms, particularly how iron-mediated lipid peroxidation induces cell death. This study, along with Dixon (eLife) [30], further explored the characteristics of ferroptosis and its role in various biological processes, and it became foundational in the field. These seminal works laid the groundwork for understanding ferroptosis mechanisms and paved the way for subsequent research, particularly in cancer therapy. Building on this foundation, Stockwell (Cell) [27] focused on applying ferroptosis to cancer treatment, particularly to overcome drug resistance. This study elucidated how regulating lipid metabolism, oxidative stress, and the antioxidant defence system can leverage the ferroptotic pathway to eradicate cancer cells, especially in cases where chemotherapy or targeted therapies have failed. Stockwell's sustained influence reflects the growing interest in ferroptosis's potential for cancer treatment.

Fig. 10.

Strictest Reference Bursts in Ferroptosis Research, Top25 References (2015–2025)

Several other key publications have further advanced our understanding of ferroptosis. Yang [9] (Cell) and Cao (Cell Molecular Life Sciences) [31] were pivotal in exploring the regulatory mechanisms of ferroptosis, particularly the roles of lipid peroxidation and GPX4. GPX4, a critical enzyme in suppressing ferroptosis, was found to trigger cell death when inhibited, leading to the accumulation of lipid peroxides. Targeting GPX4 or modulating lipid peroxidation has since become a key approach in inducing ferroptosis, particularly in cancer cells, providing a rationale for developing new anticancer therapies. Viswanathan 2017, and Doll [6] extended these mechanistic insights to clinical applications. Viswanathan explored how chemical inhibitors could modulate the ferroptotic pathway to enhance cancer cell sensitivity to treatment. Meanwhile, Doll focused on GPX4 inhibition as a potential strategy for overcoming cancer drug resistance. Together, these studies highlight the promise of ferroptosis in overcoming cancer resistance and offer new directions for clinical research.

Ferroptosis has been related not only to cancer treatment but also to several biological processes, including the metabolism of lipids and the oxidative stress (autophagy) involved in the process (including the metabolic pathways of ferroptosis) as well (for example, Kagan [32]) investigated that ferroptosis is associated to lipid metabolism especially iron-regulated lipid peroxidation causes cell death and also that the Ma (Cell Death and Disease) [33] studied that there is the interaction of ferroptosis to ferripyrite and the ferroposis that may be a factor of cancer treatment by means of autophagic pathways in the process of carcinogenesis (for example, Ma 2016) (for example, Cell Death and Disease) [33], which further broaden the knowledge of ferroptosis by proving the role of ferroptosis in general cell processes.

The research focus on ferroptosis has gradually moved from foundational research on its molecular mechanisms to actual uses in cancer therapy. The potential of ferroptosis to overcome tumor resistance has received increasing attention. Papers such as Stockwell [27] and Yang [34, 35] illustrate the growing clinical interest in ferroptosis, particularly in therapeutic settings where traditional therapies have failed. This change underlines ferroptosis's developing role as a promising target in cancer research and therapy.

Discussion

The summary of results

This paper aims to methodically investigate hotspots and areas of ferroptosis in lung cancer using bibliometric analysis. According to the findings, ferroptosis- the new method of controlled cell death- has received much attention lately because of its important role in lung cancer treatment. According to keyword co-occurrence analysis, ferroptosis has been the main focus of ferroptosis research because it has been used to treat cancer cells by causing ferroptosis; however, it also has looked at the underlying molecular processes that underlie ferroptosis, such as lipid peroxidation and GPX4 regulation. The results of these studies demonstrate the great theoretical foundation for creating new lung cancer therapy approaches and the significant possible uses of ferroptosis in more extensive studies.

Several significant research that have helped establish a solid theoretical framework for the study of ferroptosis is also revealed by examining highly cited papers and co-citation networks. The summary of results demonstrates a gradual shift in the field from foundational research on ferroptosis mechanisms to clinical applications, particularly in cancer therapy. Figure 7 shows keyword bursts such as 'GPX4,' 'oxidative stress,' and 'immune microenvironment' from 2019 to 2024 emphasize the growing interest in combining ferroptosis with immunotherapy. The co-citation network in Fig. 9 identifies seminal works by Dixon et al. [8] and Yang et al. [9] as foundational, while more recent studies focus on translational applications such as ferroptosis-targeted drug delivery systems. The focus of this evolution is on the possibility of creating new research directions for the future, especially when translating fundamental ferroptosis research into clinical practice.

Recent clinical research has begun exploring the application of ferroptosis in lung cancer treatment, focusing on overcoming drug resistance. Ferroptosis-inducing agents such as erastin and FINO2 have shown promise in preclinical models, sensitizing lung cancer cells to existing therapies by inhibiting the antioxidant defence mechanisms, particularly GPX4. Clinical trials evaluating these compounds, either alone or in combination with other therapies, are currently underway, aiming to assess their efficacy in overcoming resistance to platinum-based chemotherapy, a standard treatment for NSCLC.

The implication of future research

This paper uses bibliometric analysis in lung cancer research to clarify the important effect of ferroptosis on the lung. This information will be important in future clinical research, particularly in the personal and targeted drug development of lung cancer patients and their individualized medicine.

Development of Novel GPX4-Targeted Therapies: When the activity of GPX4 is inhibited, lipid peroxides accumulate in large quantities, eventually resulting in ferroptosis. GPX4 is crucial to the regulation of ferroptosis. The importance of GPX4 as a therapeutic target was emphasized by the fact that it was widely cited in several publications that highlighted this topic in the study. While GPX4 inhibitors remain a primary focus, future clinical research should also address other key regulators of ferroptosis. Iron metabolism pathways involving molecules like transferrin receptors and ferritinophagy-mediated ferritin degradation present new therapeutic targets. Therapies aimed at enhancing iron accumulation through ferritin degradation or transferrin receptor activation could amplify ferroptosis in cancer cells. Targeting lipid metabolism via ACSL4 activation or LPCAT3 modulation could further enhance ferroptosis induction. The development of GPX4 inhibitors should be the primary goal of future clinical research because of their potential benefits in treating lung cancer, especially in patients resistant to standard therapies. Specific ongoing clinical trials, such as those evaluating the efficacy of ML210 and RSL3, aim to assess their ability to inhibit GPX4 and selectively induce ferroptosis in tumor cells. Preclinical studies have shown that combining GPX4 inhibitors with immune checkpoint inhibitors, such as anti-PD-1/PD-L1 therapies, can enhance immune responses and overcome resistance, paving the way for novel combinatorial treatment strategies [36]. Drugs like FINO2 and deferoxamine have shown promise in preclinical models by synergizing with GPX4 inhibitors to induce ferroptosis more effectively in resistant cancer types. In addition, the multiple pathways inhibiting GPX4 have synergistic effects that enhance potency and reduce developing resistance to therapies by combining them with other targeted therapies or immunotherapies.

Ferroptosis-related Biomarkers: The study focused on ferroptosis-related biomarkers and their potential as predictive tools for therapeutic strategies. Accordingly, the bibliometric analysis revealed that the pathways of ferroptosis could reveal imperative clues regarding identification in the clinics. Future studies should prioritize the development of robust biomarkers not only for GPX4 expression but also for other ferroptosis-related pathways, such as iron metabolism and lipid peroxidation. Monitoring transferrin receptor expression or ACSL4 activity could help identify patients more likely to benefit from ferroptosis-inducing therapies. Clinical studies have begun exploring such biomarkers; for example, Doll et al. [6] identified lipid peroxidation markers as predictors of sensitivity to ferroptosis inducers in cancer cells. Yang et al. [9] demonstrated that GPX4 expression correlates with resistance to ferroptosis-inducing compounds, suggesting its potential as a therapeutic target and prognostic marker. Future studies should prioritize the development of robust biomarkers, such as GPX4 expression levels or lipid peroxidation profiles, to stratify patients for ferroptosis-based therapies. By identifying ferroptosis-related molecular signatures, clinicians can better predict patient responses and tailor treatments accordingly. Adaptive clinical trial designs integrating ferroptosis inducers with immune checkpoint inhibitors or targeted therapies should be explored to optimize combination regimens. Ongoing studies are evaluating whether ferroptosis can enhance the efficacy of PD-1/PD-L1 inhibitors in resistant non-small cell lung cancer (NSCLC), offering a promising direction for personalized treatment. Clinical trials should explore combination regimens targeting multiple pathways, such as GPX4 inhibitors alongside iron metabolism regulators or lipid peroxidation amplifiers, to maximize therapeutic efficacy [37, 28]. The combination of the GPX4 inhibitor RSL3 with the iron chelator deferoxamine [38] is under preclinical investigation to determine its synergistic effects in inducing ferroptosis. A clinical trial (NCT04882100) is exploring the combined use of ferroptosis inducers and chemotherapy in non-small cell lung cancer patients to enhance oxidative stress and overcome drug resistance. Incorporating such biomarkers into clinical trials will enable better patient stratification and optimized therapeutic outcomes.

We also recognize the importance of further exploring additional biomarkers to elucidate ferroptosis mechanisms and optimize clinical applications. Damage-associated Molecular Patterns (DAMPs), signalling molecules released during cell death, could serve as potential biomarkers for immune responses induced by ferroptosis. These molecules are critical in regulating immune cell activity within the tumor microenvironment, offering a new perspective for combining ferroptosis with immunotherapy. Similarly, oxidative stress levels, closely associated with ferroptosis, can be monitored through markers such as lipid peroxidation products or other oxidative-related molecules. These markers provide a more comprehensive understanding of ferroptosis in tumor cells and serve as precise tools for optimizing clinical treatment strategies. Together, these biomarkers predict patient responses to ferroptosis-inducing therapies and support the implementation of personalized medicine in lung cancer treatment. Further investigation into the molecular mechanisms of these biomarkers and their interactions with the immune system could enhance the clinical translation of ferroptosis inducers, offering new strategies to overcome drug resistance.

Exploring New Analytical Tools: Future studies should also explore new analytical tools to identify emerging trends and research gaps in ferroptosis-related therapies. Advanced bibliometric methods combined with artificial intelligence and machine learning algorithms, such as trend prediction models and keyword evolution analysis, could provide more accurate insights. Clustering techniques could identify latent research areas, while ML models could predict high-impact topics by analyzing citation trajectories. These approaches would enhance bibliometric accuracy and help researchers and policymakers prioritize funding and collaboration opportunities in ferroptosis research.

Role of Ferroptosis in the Tumor Microenvironment: Recent studies have demonstrated that ferroptosis modulates cancer cells and immune responses in the tumor microenvironment. Future clinical investigations should further explore how ferroptosis interacts with immune cells in the tumor microenvironment, particularly in the context of cancer immunotherapy. For example, exploring whether ferroptosis inducers can activate or enhance the function of tumor-infiltrating lymphocytes (TILs) or modulate immune responses via their effects on tumor-associated macrophages (TAMs) represents a promising avenue for future research.

Implications for clinical treatment

From a clinical point of view, this study demonstrates the important role of ferroptosis in the fight against drug resistance, improving the therapeutic effect and making it easier to use combination therapies to treat lung cancer.

Novel Research on the Treatment of Drug Resistance: The development of chemotherapy, radiation, and targeted therapy resistance is common, which greatly reduces the effectiveness of treatment. Lung cancer, especially advanced non-small cell lung cancer (NSCLC), also causes resistance to chemotherapy. According to the bibliometric analysis used in this work, ferroptosis may help deal with this difficulty. Integrating ferroptosis-targeted agents with existing therapies holds significant promise for addressing drug resistance in advanced lung cancer. Ferroptosis inducers such as erastin and shikonin have demonstrated synergistic effects when combined with platinum-based chemotherapies [39, 40], effectively enhancing oxidative stress and inducing cancer cell death. Similarly, nanoparticle delivery systems loaded with ferroptosis inducers have exhibited improved targeting of tumor cells while minimizing off-target effects. These approaches not only improve therapeutic efficacy but also provide a robust strategy to overcome resistance to conventional therapies, paving the way for more comprehensive treatment regimens.

Potential for Ferroptosis and Immunotherapy Combination: Immunotherapy has become a cornerstone in cancer treatment, with the increased application of immune checkpoint inhibitors such as anti-PD-1/PD-L1. However, not all patients respond well, and a subset of patients develops resistance in the weeks following an initial response. This study points toward a possible synergy between ferroptosis and immune responses. Further studies and clinical trials should be done to see whether ferroptosis inducers can be combined with immune checkpoint inhibitors. These combinations could enhance tumor immunogenicity, thereby improving patient immunotherapy responses and delaying or preventing immune resistance.

Possibly to combine Targeted therapy and Chemotherapy with Ferroptosis: The results of this work indicate that inducers of ferroptosis will be more efficient in a combination with already established targeted therapies or chemotherapy. While ferroptosis mostly depends on oxidative stress via lipid peroxidation, chemotherapy mainly works by causing oxidative stress to kill cancer cells. Thus, by combining ferroptosis inducers with chemotherapy, oxidative stress and cancer cell death may increase. Moreover, ferroptosis inducers may enhance current medications by inducing cell death through a different pathway, decreasing resistance in targeted therapies. In order to assess the synergistic effects of different combination therapy regimens and identify the best therapeutic combinations, future clinical trials ought to look into them.

Potential for Personalized Medicine: Bibliometric analysis indicates that the regulatory mechanisms of ferroptosis and associated biomarkers hold significant potential for personalized medicine. In clinical practice, treatment decisions could be based on a patient's gene expression profile, particularly the expression of key molecules in the ferroptosis pathway, such as GPX4. This biomarker-driven, personalized therapy could improve treatment efficacy while minimizing unnecessary side effects.

The strengths of our study

This study uses bibliometric analysis to highlight the key advantages of ferroptosis research and its relevance to lung cancer.

A comprehensive literature review and methodical analysis. The study uses the widely accepted Web of Science Core Collection, PubMed, and Scopus, which have been widely used to include excellent academic literature in various fields. The study minimizes the risk of missing important studies by using a comprehensive search strategy that ensures thorough coverage of research on ferroptosis and lung cancer. The study provides A broad academic summary, which includes several aspects of ferroptosis mechanisms and their application in lung cancer by including pertinent keywords (such as 'ferroptosis,' 'lung cancer,' and 'oxytosis'). This methodical approach makes the identification of research dynamics from several angles possible.

Advanced tools of analysis and visualization are very well known for providing detailed information about massive databases, for which VOSviewer and CiteSpace are used as bibliometric tools for detailed analysis and visualization. The co-occurrence network and the clustering function of VOSviewer analyze the research and research boundaries clear of academic relationships in different studies. CiteSpace is very good for dynamic time-series mapping, which also helps to find important studies and developmental trajectories. Using these tools, the research effectively identifies the important academic networks, the research hotspots, and the ferroptosis research. This data- driven method dramatically increases the objectivity and persuasiveness of the conclusions of this paper.

Research on multidimensional analytics Research structures, ideas, and interests: Research from the academic environment and trends related to ferroptosis and lung cancer are studied using a multi-dimensional approach, which is not based on single measurements. A detailed academic ecosystem map of very quoted papers is constructed by the analysis, which includes the publication volume, source journals, nation and institutional affiliations, keyword co-occurrence, and co-citation networks of the very cited papers. Research on the identification of key research entities (including those in particular, countries and countries, and those in which there are currently research hotspots, in the current research hotspot and the direction of new research and emergent subjects, and interdisciplinary studies) are made easier with the use of this multifaceted analysis. The methodical character of this approach not only reveals the structure of the existing body of literature but makes it abundantly evident to future research projects.

The development of collaborative studies called 'Cross-Discipline of Integrated Research': This is more closely related to cancer treatment, as it is also related to more extensive biological functions such as autophagy, oxidative stress and lipid metabolism, known as ferroptosis. The many ways in which ferroptosis and these processes interact demonstrate the many uses of ferroptosis, which is why it is used widely throughout several different scientific disciplines, according to this paper. Ferroptosis has shown considerable clinical potential since it has grown to be a central component of molecular biology, immunotherapy, metabolic control, and individualized medicine as part of the field of cancer treatment. Interdisciplinary research, especially on ferroptosis and the cancer-immune system, offers new insights into its role in the tumor microenvironment and immunotherapy. Immunologists and pharmacologists could work together to investigate how ferroptosis inducers can enhance tumor immunogenicity. Preclinical studies have demonstrated that ferroptosis can promote the release of damage-associated molecular patterns (DAMPs), which activate immune cells in the tumor microenvironment [41]. Material scientists could collaborate by developing nanoparticle-based delivery systems to target ferroptosis pathways more precisely, minimizing systemic toxicity while maximizing therapeutic outcomes. Combining the interdisciplinary knowledge base and research shows how to facilitate information exchange between domains, including biology, clinical medicine, and pharmacology. It also suggests a tendency toward collaborative research. Future clinical uses of this cross-disciplinary combination are based on a broader theoretical basis.

Analysis of the Dynamic Trend Offering insights from the Future Studies in the literature: The use of temporal and co-citation network analyses is a strength of this study, which enhances readers' understanding of the evolving research landscape. To further illustrate key findings, we have included several visual examples. For instance, Fig. 1 shows the significant increase in the volume of publications and their percentage within total research output in ferroptosis and lung cancer, emphasizing the growing focus on this area, particularly in developing novel therapies. Additionally, Fig. 6 presents a keyword co-occurrence network, highlighting the central role of "ferroptosis" in cancer research. It is closely linked to terms like "cancer," "cell death," and "apoptosis," reflecting its increasing significance. Figure 6b further illustrates the temporal development of research hotspots such as "cuproptosis" and "immunity," indicating a shift toward exploring new forms of cell death and the role of immunotherapy in cancer treatment. By incorporating these visual examples, the analysis provides numerical trends and a more transparent, accessible view of the direction in which ferroptosis research is heading, particularly in its clinical applications in lung cancer therapy.

Clinical Translation Direction: Although the main conclusions of this work are important for clinical application, bibliometric analysis mainly concentrates on academic tendencies. The gap between academic findings and clinical application remains a challenge in ferroptosis research, particularly regarding its translation into effective lung cancer therapies. Future studies should explore how ferroptosis interacts with other biological processes, including immune responses and oxidative stress, to uncover new therapeutic strategies. Several concrete strategies should be prioritized to achieve these goals of translating ferroptosis research into clinical applications. First, validating ferroptosis-specific biomarkers, such as ACSL4 expression and ferroptosis-specific damage-associated molecular patterns (DAMPs), stratifying patients most likely to benefit from ferroptosis-based therapies. Second, preclinical studies should optimize ferroptosis inducers like FIN56 and FINO2 for safety and efficacy, paving the way for phase I clinical trials targeting advanced lung cancer patients. Additionally, Combination regimens, such as GPX4 inhibitors with iron metabolism regulators or immune checkpoint inhibitors, should be explored to maximize therapeutic efficacy and overcome resistance. Advanced drug delivery systems, including nanoparticle-based platforms, can enhance precision by targeting ferroptosis pathways in the tumor microenvironment while minimizing systemic toxicity. To bridge the gap between academic findings and clinical application, prioritizing the validation of ferroptosis-related biomarkers is essential. For example, GPX4 expression levels and lipid peroxidation profiles could be validated in clinical settings to predict patient response to ferroptosis-inducing therapies. Pathways such as ACSL4-mediated lipid peroxidation and transferrin receptor-regulated iron uptake should be prioritized in drug development, as they are critical for ferroptosis initiation. Moreover, collaborative efforts between academic researchers, clinicians, and pharmaceutical companies could facilitate early-phase clinical trials, such as evaluating ferroptosis inducers like RSL3 combined with immune checkpoint inhibitors for therapy-resistant lung cancer. In the treatment of lung cancer, ferroptosis has great potential in treating cancer, especially when it comes to applying drugs in the treatment of the disease. Clinical trial design and therapeutic strategy optimization are guided by the scientific evidence provided by clinicians, which is provided by the research hotspots and boundaries that have been found. The results of the study, for example, indicate that physicians might give the development of related medications or investigate their potential in individualized treatment plans by focusing on the critical role of GPX4 inhibition in cancer therapy. Clinical researchers can also investigate combination therapies by examining the relationships between ferroptosis and other cellular processes (such as autophagy and immune responses), enabling them to find more efficient therapeutic alternatives for cancer patients.

The limitations of our study

Despite its strengths, this study has several limitations. First, the study’s timeframe spans from 2015 to 2025. As ferroptosis research rapidly evolves, this timeframe may not fully capture emerging trends. Integrating artificial intelligence (AI) and machine learning (ML) tools in future studies could address these limitations by analyzing larger datasets and predicting upcoming research trends. AI-based natural language processing could identify hidden connections between ferroptosis and other fields, enabling researchers to prioritize new interdisciplinary research areas. Second, bibliometric analysis has inherent limitations, as it does not allow for an in-depth exploration of the experimental designs or scientific content of individual studies. While bibliometric methods are valuable for identifying overarching trends within a research domain, these findings must be combined with experimental data and clinical practices to develop therapeutic strategies more effectively. Finally, mixing these two types of papers may have influenced our assessment of the substantive advancements in ferroptosis and lung cancer research. Future studies could consider a more detailed categorization of the literature to distinguish between works that primarily contribute to methodology and those that directly advance the understanding and treatment of ferroptosis in lung cancer. By making this distinction, we could better identify the specific contributions of each type of paper to the field and reduce the potential impact of methodology-focused papers on citation rate analysis.

Conclusion

Ferroptosis is a novel type of controlled cell death that has received much attention because it can be used to overcome drug resistance, explaining the molecular pathways of cancer development. We focus on the wide range of therapeutic applications of ferroptosis in lung cancer treatment, which has great promise for further approaches in the future. We conducted an in-depth study of the research dynamics, collaborative networks, and changing developments of the ferroptosis field using sophisticated tools such as VOSviewer and CitesSpace.

However, although some encouraging conclusions need to be made clear, there are some drawbacks: the limitation of data sources and the natural limitation of bibliometric analysis, which might restrict the completeness of conclusions from this study. In order to address these drawbacks, future studies should follow the fast development of such an area by including more extensive datasets and the inclusion of both experimental and clinical information in this field, and to aim at the best of ferroptosis-based therapies for lung cancer.

Author contributions

Wenhuan Song (W. Huan. Song) and Pei Pei Sun (P. Pei. Sun) took the lead in both designing the research and conducting the data analysis. Supporting this effort, Tongzhen Zhao (T. Zhen. Z), Yunxue Zang (Y. Xue. Z), Pengpeng Dong (P. Peng. D) and Qi Tang (Qi. T) contributed to the data analysis and were also responsible for visualizing the results. Wenyu Chen (W. Yu. C) and Wenyi Chen (W. Yi. C) played a key role in overseeing the methodological framework and guiding the discussion section. Zhenqing Wang (Z. Qing. W), Qinheng Zhang (Q. Heng. Z), Yinglin Wang (Y. Lin. W), and Chunhui Yin (C. Hui. Y) focused on drafting and proofreading the manuscript, ensuring its clarity and accuracy. The overall supervision of the research process, team coordination, and final manuscript review were carried out by Mingkun Yu (M. Kun. Y). All authors made significant contributions to the article and unanimously approved the final version for submission.

Funding

This study was sponsored by the China Postdoctoral Science Foundation, the Binzhou Medical University's Traditional Chinese Medicine Special Project of 2024: 2025-012, and the Binzhou City Traditional Chinese Medicine Hospital Doctoral Scientific Research Fund Project: ZYY2024BSKY02.

Data availability

All data was obtained via Web of Science Core Collection.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.