Drug repurposing in cancer research: a bibliometric analysis

Abstract

Abstract

Cancer is one of the most pressing global health challenges. Drug repurposing is regarded as the most effective strategy in developing drug candidates by using therapeutic characteristics of well-known drugs. A bibliometric analysis was conducted on drug repurposing in cancer research to assess the current state, focal points, and trends of research aimed at offering a comprehensive overview of research development and providing future research directions in the area. Utilizing the Bibliometrix R package and VOSviewer, this study examined 1166 documents indexed in the Scopus database covering the period from 2008 to 2024. The findings revealed that this field of research is steadily growing with an annual growth rate of 37.49%. The USA and China emerged as the leading contributors to research in this field, with the journals “Cancers” and “Oncotarget” emerging as the sources with the highest publications and impact, respectively. “Pantziarka P” stood out as the most prolific author, while “Bouche G” emerged as the most impactful author in drug repurposing in cancer research. Notably, subjects such as “antineoplastic activity” garnered considerable attention, highlighting critical research areas within the field. Whereas “pantoprazole” and “transwell assay” emerged as the latest trending topics in the field. Further investigations into antineoplastic agents, transwell assays, and candidate drugs such as pantoprazole are suggested for shaping the research landscape on cancer drug repurposing. The study offers valuable insights into the trajectory of drug repurposing in cancer research and provides researchers with useful guidance for future exploration of this domain.

Graphical abstract

Introduction

Cancer is one of the most pressing global health challenges [1]. It is marked by high mortality rates and a significant economic burden on the healthcare system [2]. The traditional drug discovery and development process for cancer therapy is a time-consuming and costly process with a relatively low success rate [3]. Addressing cancer therapy remains a significant challenge, as available therapies are subject to diverse challenges relating to selectivity, specificity, adverse effects, and drug resistance [4]. Hence, there is a need to develop novel treatment with high efficacy against tumors with minimal side effects [2]. Besides, the increased incidence of cancer cases has prompted the need to explore innovative therapeutic strategies, among which drug repurposing has gained significant traction [5]. Recent advances in bioinformatics [6], molecular biology [7], omics technology [8, 9], and artificial intelligence [10–12] have enabled researchers to identify potential anticancer drug targets, thus providing an excellent opportunity for repurposing FDA-approved non-cancer drugs in oncology.

Drug repurposing (repositioning, reprofiling, redirecting) is a strategy that is used to identify and develop new therapeutic uses for FDA-approved or investigational drugs that are outside the scope of the original medical indication [13–15]. New therapeutic uses are not only sought from products that are already in use but also from compounds that have been shelved, withdrawn, or abandoned because they did not perform as expected in their primary designated indications or because better therapies have emerged [16]. This strategy is largely opportunistic and by chance, as it seeks to reevaluate the promise of an existing compound against a new disease target [7]. This approach not only reduces the time and cost associated with traditional oncological drug discovery and development processes but also enhances the therapeutic landscape by identifying new applications for FDA-approved drugs with the sole aim of meeting the increased demands and unmet needs of cancer patients [17]. This strategy involves three stages: identification of the core targets of the disease (hypothesis generation), assessment of the drug effects in preclinical models, and evaluation of the drug’s efficacy in phase II clinical trials. Drug repurposing is regarded as the most effective strategy in developing drug candidates by using therapeutic characteristics of well-known drugs [18].

Bibliometric analysis is a systematic study that is carried out on scholarly articles to identify patterns, trends, and impact within a certain field [19]. Scientists use this technique to assess vast amounts of scientific data [20]. The growing interest in the field of drug repurposing for cancer research has led to an exponential growth of scholarly articles; hence, a bibliometric analysis has emerged as a pertinent method to map the intellectual landscape, identify key research trends, key players, collaboration networks, and publication patterns, and also highlight influential works that can guide future research. Understanding these dynamics is essential for framing the ongoing discourse surrounding drug repurposing in cancer research. Software such as VOSviewer, the R package ‘bibliometrix,’ and CiteSpace are the most commonly used tools in conducting bibliometric analysis [21].

Bibliometrics, based on literature data, has been extensively employed to objectively and quantitatively assess interdisciplinary connections and unveil emerging topics on drug repurposing and related fields. Examples of such studies include bibliometric analysis of drug repurposing [22], bibliometric analysis of drug repositioning [23], bibliometric analysis of aspirin drug repurposing [24], bibliometric analysis of anticancer drug prototypes in in vitro pharmacology [25], and bibliometric analysis of mapping frontiers and hot spots in anticancer research [26]. Meanwhile, bibliometric studies on drug repurposing in cancer research are scarce. Moreover, the only study found was based on the Web of Science database [27]. This study is necessary to explore the patterns of drug repurposing in cancer research using the Scopus database. Besides, Scopus is recognized as the most extensive database for citations and abstracts of global research publications [28–31]. It maintains a consistent standard for inclusion of documents in the database and possesses features that allow for easy export of bibliographic metadata for utilization in bibliometric software packages [32].

The aim of this study, therefore, was to evaluate research output on drug repurposing in cancer research over the last two decades using bibliometric science mapping and visualization tools. We analyzed the distribution of publications retrieved from the Scopus database, categorized topics, and tracked progress over time. Additionally, we examined country contributions and author collaboration (co-authorship), with particular emphasis on research topics and emerging research areas. We also highlighted important future research directions in the area.

Methods

Bibliometric method and data collection

We gathered and extracted the data for this study from the Scopus database on September 12, 2024 (Fig. 1). This database is widely recognized for its comprehensive coverage and reliable content, housing numerous publications from reputable publishers like Elsevier, Springer, MDPI, and Taylor & Francis [33, 34]. The inclusion criteria are all English research and review articles published and indexed in the Scopus database from 2005 to 2024 on drug repurposing in cancer research. The exclusion criteria include publications that meet the inclusion criteria but only mention terms like “drug repurposing” and “cancer” or their synonyms in the title, keywords, or abstract without providing substantial focused research on cancer drug repurposing.

Fig. 1.

Flow diagram of our search strategy

The following search initial string was utilized in the data retrieval: (“Cancer” OR “Tumour” OR “Tumor”) AND (“Drug repurposing” OR “Drug repositioning”). The study was streamlined to the last two decades (2005–2024) to give a clear insight into the recent research trends in the field. The search encompassed titles, abstracts, and keywords, resulting in an initial pool of 5,129 documents. Narrowing the search to research and review articles published in English gave a total of 4,586 documents. The final search string for the data retrieval was: [TITLE-ABS-KEY ((“Cancer” OR “Tumour” OR “Tumor”) AND (“Drug repurposing” OR “Drug repositioning”)) AND PUBYEAR > 2004 AND PUBYEAR < 2025 AND (LIMIT-TO (LANGUAGE, “English”)) AND (LIMIT-TO (DOCTYPE, “ar”) OR LIMIT-TO (DOCTYPE, “re”))]. Subsequently, a manual screening of the titles and abstracts was conducted to exclude publications lacking bibliometric data and those outside the subject area. The final selection of articles was meticulously curated to ensure alignment with the research scope, involving manual exclusion to achieve a focused and accurate representation of the literature relevant to the search criteria. A total of 1166 documents were manually selected and used for subsequent downstream analysis.

Data analysis

The dataset extracted from the Scopus search, consisting of 1166 documents, was saved in CSV format for further analysis. The authors utilized bibliometric software tools, specifically VOSviewer and the “Bibliometrix” R package software [35–37], along with Microsoft Excel for the analysis and result visualization. The investigators employed keyword co-occurrence network analysis to gain an in-depth overview of the current research landscape. The investigators employed VOSviewer software to generate visual maps based on key keywords, authors, and their interrelationships. Additionally, Bibliometrix facilitated the illustration of scientific trends and productivity within the documents, identifying the most prolific authors and significant articles published on the subject. This package encompasses powerful and comprehensive capabilities for bibliometric analysis, comprising analyses of authors, institutions, countries, and regions, as well as journal clustering and temporal trends [38].

Keywords are essential components of scholarly works, playing a crucial role in information retrieval and research endeavours [39]. In this study, we used VOSviewer to analyze all keywords with the full counting method, setting a minimum occurrence threshold of 5. The grouping of keywords into unique clusters indicates related terms in the dataset. The size of each term indicates the frequency of its occurrence, while the link connects keywords that co-occur in a document. The thickness of the link indicates the strength, or frequency, of the co-occurrence of two keywords in the entire dataset. Similarly, VOSviewer was used to elucidate the co-authorship-countries network, where set parameters include a maximum of 25 countries per publication and a minimum of 5 publications per country. For the thematic map and thematic evolution analysis using biblioshiny, we set the parameters to include 250 words, at least 5 clusters for every thousand documents, and 3 labels, and we used the “Walktrap” algorithm for grouping.

Though our interest was to evaluate the research on cancer drug repurposing over the past two decades (2005–2024), a number of our analyses in this study focused on the period 2012–2024. The year 2012 marks the beginning of a steady and progressive growth of publication in this field, which drew this focused attention.

Results

Descriptive statistics

The study on drug repurposing in cancer research, using the Scopus database, found that 1166 documents were published in 445 sources from 2008 to 2024, as shown in Table 1 (there were no publications in our dataset from 2005 to 2007). These publications were contributed by 6323 authors. With an annual rise of 37.49%, the overall number of publications on drug repurposing in cancer research has increased. The distribution of documents on drug repurposing in cancer research shows that out of the 1,166 documents, research articles were the most abundant documents, totaling 799, while review articles constituted the remaining 366. The international co-authorship rate stood at 30.62%.

Table 1.

The main information of the analyzed data

Description	Results
Main information about data
Timespan	2008:2024
Sources (Journals, Books, etc.)	445
Documents	1166
Annual growth rate %	37.49
Document average age	3.69
Average citations per doc	25.08
References	0
Document contents
Keywords Plus (ID)	10,268
Author’s keywords (DE)	2602
Authors
Authors	6323
Authors of single-authored docs	24
Authors collaboration
Single-authored docs	24
Co-authors per doc	7
International co-authorships %	30.62
Document types
Article	799
Review	366

Publication year

The publications’ production over time shows increased research output on drug repurposing in cancer research in the period under review. As shown in the chart (Fig. 2A), there was steady growth in publications, reflecting progressive interest in the subject. The initial growth stage reached its peak in 2016. From 2018 onward, the number of publications on drug repurposing in cancer research began to rise steadily. However, a decline in the number of publications occurred in 2022, interrupting the steady growth trend. The years 2012, 2017, and 2020 recorded the highest annual citations (Fig. 2B).

Fig. 2.

A Yearly distribution of scientific publications on drug repurposing in cancer research; B yearly average citations of scientific publications on drug repurposing in cancer research; C top 10 countries of scientific publications on drug repurposing in cancer research; D the most cited countries of scientific publications on drug repurposing in cancer research

Publication by country

Figure 2C represents the top ten countries according to number of publications. On the map, the United States and China have the highest research output on drug repurposing in cancer, with 1638 and 1569 publications, respectively, as depicted in the bar chart. The most cited countries for drug repurposing in cancer research were the United States and China, with a total of 6014 and 4287 citations, respectively, as shown in Fig. 2D. Italy, Belgium, Germany, and the United Kingdom follow with 1644, 1402, 1161, and 1124 citations, respectively. Furthermore, among the highly cited countries are India, Japan, Korea, and Australia, all with less than 1000 citations.

From Table 2, China, the United States, and India were the top 3 countries in terms of relevance estimated by the corresponding author’s country. It can be seen from the data in Table 2 that all the top 10 relevant countries had more single-country publications (SCP) than multiple-country publications (MCP). However, Egypt, Germany, and the United Kingdom dominated in the countries with a higher percentage of MCP in relation to total publications.

Table 2.

Most relevant countries of publications based on the corresponding author

Country	SCP	MCP	Articles	% SCP to total publications	% MCP to total publications
China	146	45	191	76	24
USA	133	52	185	72	28
India	82	34	116	71	29
Italy	43	19	62	69	31
Korea	32	6	38	84	16
Japan	30	6	36	83	17
United Kingdom	22	12	34	65	35
Germany	17	14	31	55	45
Portugal	29	1	30	97	3
Egypt	18	10	28	64	36

Publication by institutions

The outcome of affiliation analysis is shown in Fig. 3A, in which the most relevant affiliations of scientific publications on drug repurposing in cancer research are represented. According to the bar chart, the most relevant affiliation was Sichuan University, with a total of 90 publications. This affiliation is followed by Taipei Medical University (58 documents), Wayne State University (46), and the University of California (44 documents). Others include China Pharmaceutical University (43 documents), The University of Chicago Medical Center (40 documents), Yamagata University School of Medicine (37 documents), and Zhengzhou University (37 documents).

Fig. 3.

A The most relevant affiliations of scientific publications on drug repurposing in cancer research; B the top 10 relevant sources of scientific publications on drug repurposing in cancer research; C the source impact of scientific publications on drug repurposing in cancer research

Publications by journals

Figure 3B shows the top 10 most relevant sources out of the 445 sources on drug repurposing in cancer research, ranked according to number of documents. With a total of 46 publications, cancer emerged as the most relevant source for drug repurposing in cancer research. Among the other relevant sources included International Journal of Molecular Sciences (39 publications), Frontiers in Oncology (34 publications), Scientific Reports (31 publications), Frontiers in Pharmacology (26 publications), and Oncotarget (26 publications).

Figure 3C depicts the impact of the sources analyzed with the H index. Oncotarget, with an H-index of 22, showed the highest impact. This figure was followed by Seminars in Cancer Biology with an H index of 18. Cancers and Frontiers in Oncology both had an H index of 15. Other sources and their H indices included PLOS ONE (14), Frontiers in Pharmacology (13), E Cancer Medical Science (12), International Journal of Molecular Sciences (12), and Scientific Reports (12).

Most productive authors

Within the reviewed period, 6,323 authors contributed to publications on drug repurposing in cancer research, with 24 of them producing single-authored documents. Figure 4A presents the top-producing authors based on the number of documents they produced. Pantziarka P had the most documents, with 22 publications. Bouche G and Wang Y follow closely with 21 documents each. Other relevant authors include Vale N and Liu J, with total documents of 17 and 16, respectively. Chen Y, Li X, and Li Y had 15 documents, while Meheus L and Wang L had 14 documents each.

Fig. 4.

A The most relevant authors of scientific publications on drug repurposing in cancer research; B top authors’ productivity over time from 2012 to 2024

Figure 4B showcases the productivity of the top 10 productive authors from 2012 to 2024. Wang Y was the only author represented with a publication starting in 2012. However, his productivity extended to 2024. The productivity of Bouche G, Pantziarka P, and Meheus L started in 2014 but did not get to 2024, as no output was reported for these authors after 2022. Liu J, Li X, and Li Y were mostly productive from 2015 to 2024. Chen Y. and Wang L. started their publication in 2016 and have been productive until 2024.

Table 3 shows the impact ranking of relevant authors according to parameters such as H index, G index, M index, total citations, and publication start year (PY). The most impactful author based on H-index, M-index, and total citations was Bouche G, with an H-index of 16, an M-index of 1.455, and a total citation of 1395. Based on the G index, Pantziarka P was the most impactful, with a G index of 22 and with the highest number of publications (NP). Table 3 identified four publication start years: 2012, 2014, 2015, and 2016. We observed that the PY start for the most influential authors, Bouche G, Pantziarka P, Meheus L, and Sukhatme V, was 2014.

Table 3.

Authors with highest impact on drug repurposing in cancer research

Author	h_index	g_index	m_index	TC	NP	PY_start
Bouche G	16	21	1.455	1395	21	2014
Pantziarka P	15	22	1.364	1159	22	2014
Meheus L	13	14	1.182	942	14	2014
Sukhatme V	12	12	1.091	1033	12	2014
Sukhatme VP	12	12	1.091	1215	12	2014
Wang L	10	14	1.111	740	14	2016
Zhang L	10	14	0.769	465	14	2012
Chen Y	9	15	1	609	15	2016
Li L	9	13	1	258	13	2016
Li X	9	15	0.9	351	15	2015

Top 10 most-cited publications

Table 4 shows the top 10 most cited documents in cancer drug repurposing research according to the analyzed data set in the present study. The majority of the highly cited documents were reviews. With a total of 968 citations, Jordheim et al. [40] was the most cited document. The paper was followed by Jin and Jin [41] with 649 citations. Efferth [42] and Corsello et al. [43] had 454 and 388 citations, respectively. Roder and Thomson [44], Zhang et al. [45], Shim and Liu [46], Jahchan et al. [47], Gupta et al. [48], and Sleire et al. [49] got 385, 346, 312, 291, 272, and 244 citations, respectively.

Table 4.

Top 10 most cited documents on drug repurposing in cancer research

S/no.	Authors	Title	Journal	Total citations
1	Jordheim et al. [40]	Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases	Nature Reviews Drug Discovery	968
2	Jin and Jin [41]	The updated landscape of tumor microenvironment and drug repurposing	Signal Transduction and Targeted Therapy	649
3	Efferth [42]	From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy	Seminars in Cancer Biology	454
4	Corsello et al. [43]	Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling	Nature cancer	388
5	Roder and Thomson [44]	Auranofin: Repurposing an Old Drug for a Golden New Age	Drugs in R and D	385
6	Zhang et al. [45]	Overcoming cancer therapeutic bottleneck by drug repurposing	Signal Transduction and Targeted Therapy	346
7	Shim and Liu [46]	Recent advances in drug repositioning for the discovery of new anticancer drugs	International Journal of Biological Sciences	312
8	Jahchan et al. [47]	A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors	Cancer Discovery	291
9	Gupta et al. [48]	Cancer drug discovery by repurposing: Teaching new tricks to old dogs	Trends in Pharmacological Sciences	272
10	Sleire et al. [49]	Drug repurposing in cancer	Pharmacological Research	244

Keyword co-occurrence network analysis

Following the analysis with VOSviewer, the network map of all keyword clusters is shown in Fig. 5A. The network map identifies different clusters, displaying different items based on their occurrence. The cluster depicted in red is made up of highly occurring items, such as drug repurposing, neoplasms, metformin, and drug safety. Antineoplastic activity, human cell, apoptosis, mouse, animal experiment, and drug screening were among the most occurring words in Cluster 2 (green). The third cluster, represented in blue, is composed of diverse items with drug repositioning, genetics, bioinformatics, and gene expression profiling as the keywords with high frequency. Drug efficacy, drug mechanism, cancer stem cell, and antidiabetic agent make up the topmost occurring concepts in cluster 4, depicted in yellow. The fifth cluster (purple), has the following items in high occurrence, namely, drug delivery system, nanoparticle, liposome, and drug stability.

Fig. 5.

A All keyword co-occurrence network on drug repurposing in cancer research; B most frequent keywords in drug repurposing in cancer research

The keyword cluster analysis on repurposing drugs for cancer treatment revealed that the most frequent keyword was drug repositioning, with an occurrence of 1815 times, as highlighted in Fig. 5B. The analysis also revealed other relevant keywords such as antineoplastic agent, apoptosis, and cell proliferation, with occurrences of 625, 485, and 469, respectively.

Thematic map and evolution

Figure 6 presents the thematic map of keywords. The figure displays four quadrants. Bordering on the basic and emerging/declining themes included three concepts, namely human cell, apoptosis, and metabolism. The motor themes highlight concepts that closely link to the basic quadrant, such as drug repositioning, antineoplastic agents, and antineoplastic activity. In the top left quadrant, neoplasms, and breast cancer were the research themes found in the thematic map.

Fig. 6.

Thematic map illustrating notable themes related to drug repurposing in cancer research

The trend topics and research concepts based on keywords from drug repurposing in cancer research are depicted in Fig. 7. Drug-based management of malignant neoplastic diseases, side effects, and animal studies dominated the research landscape between 2012 and 2018. However, the trending topics between 2020 and 2024 included antineoplastic agents, drug repositioning, molecular dynamics, molecular docking, differential gene expression, repurposing, pantoprazole, and transcriptome.

Fig. 7.

Trend topics based on keywords plus on drug repurposing in cancer research

Countries’ collaboration network

The network map of co-authorship among countries for drug repurposing in cancer research is shown in Fig. 8. Eight (8) clusters represented with different colours, curved lines, and nodes can be observed from the network map. The most captivating aspect of this map is the elaborate interconnections among the countries represented by the curved lines. The United States and China were reportedly dominant in these interconnections, as depicted in the larger sizes of their nodes.

Fig. 8.

Network of the co-authorship countries on drug repurposing in cancer research

Discussion

Using scientific literature records from the Scopus database, we conducted an in-depth bibliometric analysis of the research output on drug repurposing in cancer research from 2008 to 2024. Critical consideration was given to the field’s worldwide research trends, which included research hotspots, important contributors, conceptual development, and anticipated future research. The findings showed that knowledge in this area has advanced quickly during the past 16 years. This rate of increase (37.47%) indicates that the body of knowledge is growing gradually. The discipline is dynamic, as evidenced by the introduction of novel concepts, investigations, and deductions every year. Similarly, the international co-authorship percentage (30.62) highlights considerable global networking in generating scientific information on drug repurposing in cancer research. This figure indicates that international collaboration is responsible for at least one out of every three publications on drug repurposing in cancer research, thus increasing the variety of viewpoints, skills, and funding invested into its research. Due to their wide coverage and impact, research articles and reviews are the most common means of publishing scientific information, as reflected in the present findings. Similarly, Bali [27] also reported that research articles were more numerous than review articles, which agrees with this study.

Research interests on drug repurposing in cancer research have grown, resulting in an annual increase in publications. This increase in research is similar to what Bali [27] found, where he noticed significant yearly growth, especially in 2020 and 2021, by analyzing publication data from Web of Science between 2012 and 2021. This yearly increase reported by Bali [27] and observed in this study may be attributed to factors like the COVID-19 pandemic, which saw wide repurposing of conventional drugs for the treatment of the viral disease. Meanwhile, the observed general growth in yearly publication may be associated with increasing research interest in cancer chemotherapy, which has gained wide and increasing research attention. The pandemic also influenced the allocation of more funds for drug discovery which might have boosted research on drug repurposing for cancer treatment. Figure 2B shows that scientific publications on drug repurposing in cancer research received significant yearly average citations. The peak average citation in 2013 could be linked to the initial growth phase of publication production in the research field in the reviewed period.

The United States and China dominated the research output and citations on drug repurposing in cancer. Likewise, the analysis by Bali [27] reported the United States as the most productive country in drug repurposing for cancer treatment. The global distribution seen from this study highlights that research on drug repurposing in cancer research is localized in countries with scientific and technological advancements for cancer therapeutics. The high number of citations from the United States and China corresponds with the large volume of publications emanating from these countries on drug repurposing in cancer research. Consequently, these countries can be regarded as leaders in drug repurposing in cancer research. The top 10 most cited countries represent the global hotspots for drug repurposing in cancer research.

The nation of the corresponding author serves as an illustration for comprehending leadership and teamwork in the international research environment. In terms of the corresponding author’s country, the presence of China and the United States as the top countries aligns with the previous observation that China and the United States were the most cited and most productive countries. Articles fall into two categories: single-country publications (SCP), which are documents with all authors from the same nation and indicate intra-country partnership, and multiple-country publications (MCP), which are papers with contributors from various nations and symbolize inter-country exchanges [50]. Several factors could explain the observation that all the top 10 relevant countries had more SCP than MCP. Given the common language, cultural backgrounds, time zones, and regulatory structures, research partnerships inside a given nation are typically simpler to sustain. To create a robust scholarly environment, nations that focus on developing national technological capabilities may prioritize indigenous research. Laws that restrict cross-border cooperation govern certain research fields, especially those that deal with vital innovations or information. Another important finding is that articles from China dominated the SCP, while the United States had the highest MCP. Possible explanations for such differences might border on openness and ease of knowledge sharing, which are in turn influenced by cultural and institutional factors in these countries. The present findings also suggest that Egypt, Germany, and the United Kingdom may serve as key locations for international collaboration due to their higher prevalence of MCP compared to SCP.

Apart from its use in analyzing worldwide networking and knowledge sharing, country co-authorship is also useful in estimating the impact and quality of research ventures. The elaborate interconnections among the countries reflect the extensive inter-country collaboration and are in line with the significant international co-authorship reported earlier. Another observation on the network map worthy of note is the size of the nodes, reflecting the total link strength. The United States and China were the dominant countries. It can be further inferred that these countries are key hubs for research linkages due to their numerous links and strong influence on drug repurposing in cancer research.

Authors are usually affiliated with institutions or organizations from which they conduct their research. Thus, affiliations are useful in bibliometric analyses for evaluating research trends and institutional output in a given body of knowledge. Consequently, Sichuan University, Taipei Medical University, Wayne State University, the University of California, China Pharmaceutical University, the University of Chicago Medical Center, Yamagata University School of Medicine, and Zhengzhou University ranked high from this investigation. These affiliations are located in the countries that have significant output in drug repurposing for cancer research. This trend shows that these institutions are relevant centers for drug repurposing in cancer research funding, collaboration, and policymaking.

Scientific information is usually published in sources such as journals and conference proceedings. The present study found that Cancers, with a total of 46 publications, was the most relevant source for drug repurposing in cancer research. Similarly, Bali [27] highlighted that Cancers was the most active journal according to the number of research articles on the subject matter. Cancers is published by Multidisciplinary Digital Publishing Institute (MDPI). With a 5-year impact factor of 4.9 recorded in 2023, Cancers is a global, freely accessible, peer-reviewed oncology journal that publishes original research papers, reviews, opinions, and short communications on basic, translational, and clinical investigations across all kinds of cancers [51]. The many articles about drug repurposing in cancer research from Cancers may be due to its unique policy of accepting research with important but negative results, which most journals do not allow. This acceptance of such unfavorable findings encourages researchers to disseminate the information so that others can avoid repeating previously conducted tests [52]. The different sources on drug repurposing in cancer research show that more and more researchers from various fields are interested in this topic, and journals provide fast and helpful ways to share the latest scientific information and studies on cancer drug repurposing.

The H-index is a metric designed to measure both the productivity and influence of sources and researchers’ academic contributions through the dual lens of publication quantity and citation impact. Specifically, a source or researcher has an H-index of h if they have published at least h papers, each of which has been cited at least h times. The relevance of influential journals in drug repurposing in cancer research varies in their number of publications and impact. Despite the large number of documents from Cancers, it was not the most impactful source. However, with only 26 publications, Oncotarget was the most impactful according to the H-index. Impact Journals LLC, an affiliate of the Society for Scholarly Publishing, established Oncotarget in 2010 and publishes it. By connecting many areas of cancer studies and biomedical sciences, Oncotarget, an open-access journal with a primary emphasis on oncology, seeks to erase boundaries between disciplines and optimize research effect through critical peer review [53]. This rigour of the peer-review process could have led to the differences in the impact of these top-ranking sources.

Among the most influential authors, Pantziarka P ranked high in number of publications. The study by Pantziarka P in 2021 focused on procedures for designing a functional and accessible database for cancer drug repurposing clinical trials [54] and is relevant in shaping the cancer research landscape. Accordingly, information about clinical trials that reconfigure medications that were first approved for non-cancer reasons or different cancer types to novel oncology-related uses was compiled in the database. It combined trial data from multiple sources and is a useful tool for promoting cooperation, accelerating drug repurposing initiatives, and shortening the time for market entry for innovative cancer treatments. As pointed out earlier, significant collaboration among the authors was observed and can be noted in the list of authors in most of the documents reviewed. In comparison with the study by Bali [27], Pantziarka P was reportedly the most productive in publication contributions.

The H index compares publications and citations and uses it to analyze the performance and impact of an author [55]. The use of the H-index stems from its capacity to balance quantity with quality in scholarly output. Unlike simply counting the number of publications, which might favor prolific but perhaps less impactful authors, the H-index emphasizes contributions that have garnered significant attention within the academic community. Consequently, it has gained widespread acceptance as a standardized measure of research output across various fields. The G-index is a significant H-type index because it captures the inputs from frequently cited articles in addition to maintaining most of the H-index’s benefits [56]. The M-index enables cross-comparing academics at various career points [57]. In the current study, Bouche G was the most impactful, with an H index of 16. Most of the influential authors, including Bouche G, Pantziarka P, Meheus L, and Sukhatme V, began their publication years (PY) in 2014, which corresponds to the period of initial growth in drug repurposing for cancer management. This evidence further suggests that these authors contributed significantly to the foundational development of the field of study.

Interestingly, the significant authors have contributed to diverse aspects of research and correspondence on cancer drug repurposing within the period of their peak publication production. For instance, Bouche G [58] has contributed to many research articles on cancer drug repurposing, primarily collaborating with Pantziarka P, although he is not listed as the first author. However, in a correspondence article, Bouche G pointed out the growing interest in using non-cancer drugs for cancer treatment and the use of computer tools to find possible new drug candidates, while also mentioning the challenges of getting regulatory approvals and protecting intellectual property when trying to use repurposed drugs in research and clinical settings. Given the low prevalence and significant genetic variability of uncommon malignancies, Pantziarka and Meheus [59] investigated the possibility of repurposing current medications for their treatment utilizing omics-related data. As a result, they explained the potentials of repurposing in the management of rare diseases such as sino-nasal tumors, ovarian clear cell carcinoma, and angiosarcoma. Chen and Xu [60] used a combination of mice phenotypic information and human genetics to formulate a medication repurposing strategy for glioblastoma and associated genetic variants. Their methodology also revealed promising treatment possibilities for glioblastoma and its various forms.

The majority of the highly cited documents were reviews, indicating an association between higher citations and review papers. We present a summary of the contributions of some of the most cited papers. To evaluate cancer drug development, Jordheim et al. [40], in the most cited document, reviewed novel nucleoside equivalents and related drugs undergoing preclinical or clinical trial stages for the management of viral-borne illnesses and cancers. Numerous derivatives of nucleosides and nucleotides have undergone pharmacological repositioning as several of these substances once authorized as antiviral medications show promise as cancer therapies. The authors illustrated cancer drug repurposing with trifluorothymidine. Originally created as an antiviral drug, trifluorothymidine blocks thymidylate synthase and causes double-stranded DNA breakage. Trifluorothymidine and the thymidine phosphorylase blocker tipiracil have been combined for therapeutic usage, leading to significant survival rates in a Phase II trial involving metastatic colorectal cancer patients.

A revised picture of the tumor microenvironment was provided by Jin and Jin [41], who focused on its mechanical, immunological, metabolic, connected, and oxygen-deprived domains. These aspects are critical in understanding tumors and designing effective drugs. Additionally, they provided an overview of the prospective use of common medications such as aspirin, celecoxib, metformin, β-adrenergic antagonists, and statins in novel anticancer applications. Based on their anticancer efficacy and widespread clinical applications, these medications are regarded as promising options for therapeutic combinations. The authors inferred that the tumor microenvironment is a complex ecosystem that is heterogeneous and can impact nearly every facet of cancer science. They also concluded that as our knowledge of the tumor microenvironment advances, cancer treatment will get simpler.

The study by Corsello et al. [43] targeted providing a publicly accessible repository that would list the growth-inhibitory effect of 4,518 non-cancer medications that were tested on 578 human cancer cell lines. To screen medications against cell types in pools, they employed a molecular barcoding technique called PRISM (profiling relative inhibition simultaneously in mixtures). Numerous non-oncology medications preferentially suppressed groups of cancer cell lines. Among the substances they discovered were those that caused the synthesis of the phosphodiesterase 3 A-Schlafen 12 complex, vanadium-containing substances whose destruction was dependent on the sulfate transporter SLC26A2, the alcohol-dependent medication disulfiram, which killed cells with low metallothionein expression, and the anti-inflammatory medication tepoxalin, which was potent through the multidrug resistance protein ATP-binding cassette subdomain B member 1 (ABCB1).

Furthermore, Roder and Thomson [44] examined the modernization of the ancient medication auranofin. A medication called auranofin has been licensed for the management of rheumatoid arthritis, but it is also being researched for possible therapeutic use in various other illnesses, such as cancer. Auranofin’s primary mode of action involves inhibiting redox (reduction/oxidation) enzymes, which are necessary to sustain subcellular reactive oxygen species concentrations. Oxidative damage and spontaneous cell death result from suppression of these enzymes. Similarly, Liu et al. [61] reported that Auranofin causes apoptosis in cancer cell lines from patients with acute myeloid leukemia and specifically suppresses tumor development.

Finally, Jahchan et al. [47] identified potential FDA-approved medications for the treatment of small cell lung cancer by using a comprehensive drug repositioning bioinformatics technique that involved querying a sizable database of gene expression patterns. They discovered that tricyclic antidepressants and related compounds effectively trigger cell death in human and mouse lung tumors transferred into immune-deficient mice. The potential medications block autocrine survival signals involving neurotransmitters and their G protein-coupled receptors, which in turn triggers stress pathways and causes lung cancer cells to die. Merkel cell carcinoma and pancreatic neuroendocrine tumors are among the other neuroendocrine cancers whose growth is inhibited by the potential medications.

It can be deduced that the most cited studies focused on the potentials of repurposing drugs towards cancer therapy. Although these drugs might be indicated for diseases other than cancer, their mechanisms of action can be harnessed in treating cancer. This approach has the advantage of saving investments into new drug discovery, characterization, and trials, as these candidate drugs have been previously screened for efficacy and safety.

Analyzing the keyword cluster is key to understanding the structure and components of knowledge in each field. The commonly appearing keywords, including drug repurposing, drug repositioning, antineoplastic activity, drug screening, drug mechanism, and drug delivery system, are very relevant as they reveal information about the framework, patterns, and elements of the research on repurposing drugs for cancer treatment. Thus, the research efforts in the field under review have primarily focused on cancers, the need to find cancer treatment applications for non-cancer drugs, the use of animal and human models, pharmacodynamics, and genetics. The antineoplastic roles of anticancer agents are key concepts of cancer therapeutics and are further reflected in the multiple occurrences of terms such as antineoplastic activity and antineoplastic agents. In line with the actions of anticancer agents for targeting cells and mediating their therapeutic functions, themes such as human cell, signal transduction, metabolism, and drug effect were also observed as part of the dominant keywords in the data set.

Our study mapped the evolution of knowledge about drug repurposing in cancer research. The concepts noted in the basic theme included human cells, apoptosis, and metabolism. They are central and relevant, covering the fundamental topics and basic frameworks connecting the field of cancer drug repurposing. Thus, they clearly reflect the mainstay of research interest in cancer therapeutics. The motor themes located at the top right quadrant point to the important research areas pertinent for advancing the research on a given field, having potential for impactful research. The motor concepts include drug repositioning, antineoplastic agents, and antineoplastic activity, all of which are highly relevant for understanding drug repurposing and its connections to anticancer activity. Furthermore, these topics were covered in the most cited research documents, pointing to some level of development of the field. At the top left quadrant were neoplasms and breast cancer, which can be considered well-developed and specialized themes. The relevance of these concepts is in the practical applications of drug repurposing in the treatment of breast cancer and other neoplasms.

From 2012 to 2024, diverse topics have been the focus of research in the field of study. This diversity of research topics reflects a multidisciplinary perspective in which disciplines such as pharmacology, genetics, genomics, molecular biology, cell biology, toxicology, and biochemistry contribute to the evolution of knowledge on drug repurposing for cancer management. The presence of antineoplastic agents, drug repositioning, molecular dynamics, molecular docking, differential gene expression, repurposing, pantoprazole, and transcriptome among the trending topics suggests a shift towards understanding the antineoplastic actions of repurposed drugs at the molecular and gene expression levels. Accordingly, a recent work by Shaikh et al. [62] provides an example of this transition, reporting the repurposing of pharmaceuticals for the treatment of cancer using several tools and techniques based on structure and ligand similarities, including dynamics modeling, simulated screening, and molecular docking.

Future research directions

Research advances on drug repurposing in cancer, particularly its potential to identify new effective therapeutic agents, present great prospects for expanding future investigations in this area. An important aspect of further research is the study of antineoplastic agents. Antineoplastic agents are used in cancer chemotherapy through diverse mechanisms such as targeting the impairments of signal transduction and DNA regulation [63]. This raises shortcomings in the efficacy of these agents. Therefore, there is a pressing need for novel antineoplastic agents, originating from both chemical synthesis and phytochemicals [64]. Drug repurposing has emerged as a potent alternative technique to find and formulate new anticancer compounds from the current pool of drugs, following the effective introduction of several non-cancer medications for the treatment of cancer [46]. Efforts are needed to identify new antineoplastic drugs from non-cancer drugs and elucidate their mechanisms of action. The molecular targets of these agents need to be identified. These efforts could potentially find new applications and indications for existing drugs, reducing economic investment in new chemical syntheses and their associated side effects.

Another effort for advancing the frontiers of cancer drug repurposing research is the transwell assay. By detecting the chemotactic migration of cells via the transwell membrane, the transwell test is a proven in vitro technique for evaluating the ability of tumor cells to spread [65]. This experiment is frequently used to investigate chemotaxis and cell mobility. Its applicability in cancer therapy medication repurposing stems from its capacity to evaluate how pharmaceuticals, both new and old, affect the actions of tumor cells, especially during crucial physiological processes such as the spread of cancer cells. Several studies on cancer drug repurposing have applied the transwell experiment in their investigations [66–68]. Despite the usefulness of the transwell assay, there are areas for further research to derive maximum utility for cancer biology, especially in drug repurposing [69]. These include proper mimicry of the tumor microenvironment in the assay, integration of omics and high-throughput techniques, and investigating tumor-immune cell interactions.

Furthermore, one of the trend topics that we consider relevant for shaping the prospects of drug repurposing for cancer treatment is the use of the antacid pantoprazole. Pantoprazol which is a widely utilized proton pump inhibitors (PPIs) for treatment of gastric acid-related disorders, have been demonstrated to be useful in cancer prevention by inducing cell death in a variety of tumor cell lines [70]. Zeng et al. [71] found that intraperitoneal injection of pantoprazole inhibited progression of cancer in HCT 116 colonic tumor-bearing mice. Whereas, other research provides contradictory results. For instance, in a phase I/II randomized controlled trial, individuals with severe squamous-cell carcinoma of the head and neck did not have better results when intravenous pantoprazole (240 mg) was added to systemic therapy [72]. However, recent studies have generally highlighted its potential repurposing as an adjunct therapy in oncology due to its reported effects on cancer cell biology. For instance, studies have suggested that pantoprazole, alongside other PPIs, may influence cancer cell proliferation and autophagic processes, presenting novel avenues for cancer treatment [73, 74]. The implications of such findings warrant further investigation into the mechanistic pathways by which pantoprazole affects tumor biology, particularly its role in autophagy and apoptosis of malignant cells.

Clinical safety remains a significant consideration in the practical application of pantoprazole, particularly in inpatient settings. Research has documented a low incidence of adverse effects in certain populations, yet concerns regarding potential complications such as acute interstitial nephritis, hypomagnesemia, and various gastrointestinal issues persist [75, 76]. Such side effects underscore the importance of further studies to ascertain the long-term safety profile of pantoprazole as cancer treatment. Future research should prioritize the exploration of pantoprazole’s interaction with other medications, especially in polypharmacy contexts commonly encountered in elderly populations and patients with multiple comorbidities. A deeper understanding of these interactions could lead to refined clinical guidelines that enhance patient safety while maximizing therapeutic efficacy [77, 78]. Furthermore, ongoing investigations focusing on the root physiological mechanisms enabling pantoprazole’s diverse clinical applications, particularly its role in modulating the immune response, warrant increased scholarly attention. Such research could pave the way toward innovative uses of pantoprazole in areas currently not associated with acid inhibition, expanding its utility in medical practice and potentially leading to improved patient outcomes in various therapeutics [74, 79].

Emerging research highlights pantoprazole’s implications in oncology, necessitating a comprehensive assessment of its pharmacokinetic characteristics, clinical safety, and interaction profiles. Future investigations should therefore be multifaceted, focusing on both the mechanistic and clinical implications of pantoprazole, paving the way for its effective utilization across a broader array of medical contexts. Further studies on pantoprazole’s repurposing in cancer treatment should examine the underlying mechanisms of its activity in relation to apoptosis and tumor microenvironment regulation, explore its use in combined treatment options, investigate its dosage and delivery routes, and assess its clinical effectiveness in treating various cancer types.

Limitations

Despite providing vital information about cancer drug repurposing research around the world, this study has some drawbacks. By focusing solely on the Scopus database, the study excluded many other important databases, such as Web of Science, Google Scholar, Dimensions, and Lens. While the exclusion may appear as a drawback, the Scopus database is widely considered the most reliable source for scholarly articles. However, this database might have limited access to a wider range of documents published in the subject area. This implies missing out on some relevant publication in the subject area. Moreover, the usage of English-language publications is another restriction. In light of this, the results may be skewed toward English-based authors and sources, omitting other pertinent ones. This limitation also implies that the study does not represent relevant research in this subject area from a non-English background. Future studies on cancer drug repurposing research development should address these shortcomings and lessen biases. Despite these limitations, the study’s validity and utility remain untouched, providing important information regarding the current and possible future directions of drug repurposing in cancer treatment and research globally.

Conclusion

Bibliometric analysis was employed to examine the yearly publications, prolific authors, prominent journals, contributing nations, popular keywords, general progress, and evolution in drug repurposing in cancer research from 2005 to 2024. This paper is the first to analyze the topic using a bibliometric approach based on the Scopus database, which provides a thorough assessment of research output in the field that includes analysis of authors, sources, documents, themes, research trends, and future research focus. 6323 authors from diverse institutions across the globe contributed to the publications analyzed in this study. With an annual rise of 37.49%, the body of knowledge is growing steadily. Furthermore, the international co-authorship percentage (30.62%) highlights significant global networking in generating scientific information on repurposing drugs for cancer treatment. The United States and China were the most productive and most cited countries, while the United States had the highest global collaboration. Cancer was the most productive source, while Oncotarget was the most impactful. Pantziarka P is the most productive author, while Bouche G emerged as the most impactful author in the field. We identified the concepts of antineoplastic agents and antineoplastic activity as crucial for comprehending drug repurposing and its relationship to anticancer activity. We suggest more research on antineoplastic agents, transwell assays, and potential drugs like pantoprazole to improve the study of cancer drug repurposing. Drug repurposing has been extensively applied to cancer types like breast cancer, colon cancer, and lung cancer. It has also been applied to pancreatic, brain, stomach, liver, and prostate cancer to a comparatively lesser degree. This bibliometric study has identified the current global trends that can shape future research on cancer drug repurposing.

Author contributions

Conceptualization: Uche Samue Ndidi. Methodology: Israel Ogwuche Ogra, Emohchonne Utos Jonathan. Formal analysis and investigation: Israel Ogwuche Ogra, Okechukwu Kalu Iroha. Data curation: Israel Ogwuche Ogra, Emohchonne Utos Jonathan, Okechukwu Kalu Iroha, Uche Samue Ndidi. Writing—original draft preparation: Okechukwu Kalu Iroha, Emohchonne Utos Jonathan, Israel Ogwuche Ogra; Writing—review and editing: Israel Ogwuche Ogra, Uche Samue Ndidi. Supervision: Uche Samue Ndidi. All data supporting the findings of this study are available within the article and as supplementary files.

Funding

No funding was received for this research.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Competing interests

The authors have no conflict of interest to declare that are relevant to the content of this article.

Ethical approval and consent to participate

No aspect of our research required formal ethical approval or usage of participants.

Clinical trial number

Not applicable.

Consent for publication

The authors agree on the transfer of the copyright to the Publisher on acceptance of this manuscript for publication.