Cancer research in Lebanon: Scope of the most recent publications of an academic institution (Review)

Abstract

Cancer may be considered one of the most interesting areas of study, and although oncology research has grown markedly over the last decade, there is as yet no known cure for cancer. The objective of the present review is to examine various approaches to cancer research from a single institution, summarize their key conclusions and offer recommendations for future evaluations. The review examined 72 cancer-associated studies that were published within six years from 2017 to 2022. Published works in the subject fields of ‘cancer’ or ‘oncology’ and ‘research’ that were indexed in Scopus and Web of Science were retrieved and sorted according to article title, author names, author count, citation count and key words. After screening, a total of 28 in vitro/animal studies and 46 patient-associated published studies were obtained. A large proportion of these studies comprised literature reviews (20/72), while 20 studies were observational in nature. The 72 publications included 23 in which various types of cancer were examined, while the remaining studies focused on specific types of cancer, including lung, breast, colon and brain cancer. These studies aimed to investigate the incidence, prevalence, treatment and prevention mechanisms associated with cancer. Despite the existence of extensive cancer research, scientists seldom contemplate an ultimate cure for cancer. However, it is crucial to continuously pursue research on cancer prevention and treatment in order to enhance the effectiveness and minimize potential side effects of cancer therapy.

1. Introduction

Cancer poses an important global public health challenge and ranks as the second leading cause of death worldwide, following heart diseases. The American Association of Cancer Research states that the primary objective of the study of cancer is the development of safe and effective approaches for the prevention, detection, diagnosis, treatment and cure of this disease (1). Advancing the understanding of cancer, including its treatment options, preventive measures and psychological impact, is crucial for making substantial progress in the reduction of its profound human and economic toll on the well-being of patients. Enormous sums of money have been spent on cancer research worldwide (2). However, due to extensive exposure to numerous environmental chemicals in everyday life and the complex nature of chemical mixtures (3), it is challenging for long-term safety evaluations to provide perpetual true results concerning cancer diagnosis and treatment as well as accurate updates. An ultimate cure for cancer remains the top aim of numerous researchers (4). Despite the marked increase in cancer research and the substantial growth in the number of cancer survivors over the past three decades, it is undeniable that the global occurrence of this disease continues to rise (5). Regarding cancer survival, it has been reported that during the last decade half of the individuals diagnosed with cancer in England survived their disease for ≥10 years (6). While there have been numerous advancements in the pharmacological treatments of tumors, and new highly sensitive techniques for the early diagnosis of pathologies, including imaging, laboratory tests, tumor biopsy, endoscopic examination, surgery, genetic testing and microfluidic systems have been developed (7,8), a definite cure for cancer remains elusive. Nevertheless, researchers persist in their efforts to develop new and more effective treatments and preventive measures for cancer. For example, long-term epidemiological studies have identified specific risk factors, such as the maintenance of a healthy weight, avoidance of tobacco, limitation of alcohol intake and protection of the skin that, if reduced, can prevent the development of certain types of cancers (9,10). Moreover, cancer risk prediction models based on these epidemiologic data have identified the risk of an individual carrying a genetic mutation for a specific cancer, such as BRCA 1 and/or BRCA 2 (11). Additionally, several innovative treatments, including hormonal therapy, monoclonal antibodies and chimeric antigen receptor T-cell therapy (12), are already being used alongside more traditional cancer therapies. Research efforts are now particularly focused on the role of gene editing and nanoparticles in combating cancer cells (13). Furthermore, a recent breakthrough in our understanding of the regulatory functions of small RNAs, originally discovered in plants, is providing new insights into the biology of cancer (14). Despite the clear rational and contemporary interest in cancer research, its assessment comes with challenges. Firstly, despite the recent surge in interest, there remains a lack of knowledge regarding the most effective methods for conducting research assessments (15). Secondly, in 2020, updates on the diagnosis and treatment of cancer were negatively impacted by the coronavirus disease (COVID)-19 pandemic. Restrictive measures and the closure of healthcare settings during the pandemic led to limited access to care, resulting in delays to cancer diagnosis, treatment and research updates regarding cancer incidence and etiologies (16). In Lebanon, particularly at the Lebanese American University (LAU), several scientific studies were conducted to explore new cancer therapies and preventive measures (17–20). However, according to a 2021 report from the Global Cancer Observatory of the National Cancer Registry, there were 11,589 new cancer cases and 6,438 cancer-related deaths in Lebanon in 2020 (21). One notable finding is the absence of data on the survival rate of cancer cases in the official Lebanese registry maintained by the Lebanese Ministry of Public Health (22).

Hence, the objectives of the present review are to examine cancer research methodologies documented in LAU libraries, with a particular focus on publications following the outbreak of COVID-19, assess these methodologies, consolidate their key findings and provide recommendations for future assessments. The present study encompasses various aspects of cancer research, including fundamental laboratory investigations and human studies, as well as basic scientific and applied research. It encompasses research pertaining to pediatric or adult cancer, as well as studies spanning the nursing, medical and public health aspects of cancer research. Consequently, the study seeks to achieve the following: i) Identify existing literature reviews that document approaches to the assessment of research impact and summarize these approaches; ii) summarize the findings of each study based on different cancer types; and iii) make recommendations to steer future cancer research towards addressing the specific requirements of the Lebanese population.

2. Study retrieval

The present study focused on the analysis of publications from the LAU (Beirut, Lebanon) over the past 5 years, specifically from 2017 to 2022. These publications were selected as a representative sample of a Middle Eastern academic and medical research center. During this time period, the School of Pharmacy and the School of Medicine at LAU actively participated in cancer research, conducted studies and stayed up-to-date with the latest advancements. The dataset used for analysis was obtained from SciVal (https://librairies.lau.edu.lb/research/databases/?index=S#id_libdbform), a research performance assessment tool that facilitates the analysis of data from Scopus and Web of Science (WOS). While there were variations in coverage between these two indices, the present study considered articles that appeared in both to provide a broader perspective on the correlation between citation count and author number. The study of published cancer research at LAU is based on the collaborative efforts between academic researchers and medical physicians. The search was initiated under ‘all subject areas’ and then proceeded using specific themes such as ‘medicine’ and ‘cancer research’. Published works were also extracted with specific keywords such as ‘neo*’, ‘tumor’, ‘cancer’, ‘oncol*’, ‘leukem*’, ‘lymph*’, ‘chemo*’ and ‘radio*’ as individual topics. The search in the category ‘institutions and groups’ was limited to ‘The Lebanese American University’; Lebanon was the country of choice in the category ‘countries/regions’ and the date limits were ‘2017–2022’. The data obtained from SciVal included i) article title, ii) author names, iii) author count, iv) citation count, v) field-weighted citation impact, and vi) CiteScore (CS). Bibliometric analysis was performed to compare the published works in the present study. In order to achieve this objective, the CS was used as the primary method for counting citations (23,24). The present review only included published articles and focused exclusively on peer-reviewed journals, even though the selection of journals may vary depending on the citation-based metric system being considered, resulting in different quartiles. No restrictions were made regarding author names and collaborations. Additionally, single- and hyper-authored publications, abstracts only, studies written in a language other than English, corrections to previous studies, errata, conference proceedings and book series were excluded.

Nearly all the published research from the specified years were included in the present study. To ensure accuracy and relevance, two independent reviewers conducted a thorough screening of all records based on the topic search. The screening process involved reviewing study titles for potential relevance to cancer research and examining the full-text articles for specific references to cancer.

3. Study design and setting

Between 2017 and 2022, a total of 2,137 research works by LAU were published in journals indexed in Scopus and WOS, covering various research fields. Out of these, 252 studies specifically focused on cancer research. Following the PRISMA guidelines, a thorough screening process was conducted based on the titles and abstracts of the publications as depicted in Fig. 1. After removing duplicates, corrections and errata, 124 papers remained for full-text review. Ultimately, 72 studies were deemed eligible and met the inclusion criteria. The number of publications gradually increased from 2017 until 2021, reaching its peak in 2020, when 26.3% of the studies were published and remained constant in 2021. However, the number of papers published dropped in 2022 (Fig. 2), comprising only 8.3% of the studies in this time period. Among the 72 publications, 25 focused on in vitro or animal studies, while 47 were patient-associated studies.

Figure 1.

Diagram of the study selection process. LAU, Lebanese American University; WOS, Web of Science.

Figure 2.

Percentage of cancer-associated publications per year.

Considering the patient-associated studies, the highest proportion were literature reviews (18/72), followed by 5 systematic reviews, 1 meta-analysis and 22 observational studies of a cross-sectional, cohort or case-control nature. In addition, there was one interventional randomized controlled study. Fig. 3 provides an overview of the types of cancer studies reported by the LAU directory. Notably, two studies specifically targeted fetal cancer and metastasis, and involved pregnant women. Furthermore, five studies were conducted on the pediatric population.

Figure 3.

Types of studies included in the Lebanese American University research directory between 2017 and 2022.

4. Types of cancer and main endpoint

The faculty at LAU conducted research on various types of cancer. Some of these studies specifically investigated new herbal treatments and examined their anticancer properties (7/72 publications). In total, 28 of the 72 publications examined multiple cancer types or cancer in general. The primary objectives of these studies were twofold: Firstly, to explore pharmacological mechanisms and highlight pathways for cancer prevention (39.1%); and secondly, to evaluate the psychological challenges associated with cancer (30.4%). One study specifically focused on the identification of potential risk factors associated with cancer (5). The remaining studies each focused on specific types of cancer, such as lung, breast, colon or brain cancer. The main objectives of these studies were to investigate the incidence, prevalence, treatment options and prevention mechanisms for these specific types of cancer. Studies that focused on understanding the regulatory functions of small RNAs and human recombinant arginase I in the treatment of cancer constituted only 4.16% of all publications and were all published in 2020 (25–27). Additionally, several in vitro studies were conducted, which examined either a variety of cancer types or specific types of cancer. More comprehensive information on the various types of cancer researched is presented in Fig. 4.

Figure 4.

Types of cancer studied at the Lebanese American University between 2017 and 2022.

5. Detailed description of LAU cancer studies

In the LAU dataset of 72 cancer publications, 38.89% covered all types of cancer, as indicated in Table I (18,28–53), while the remaining 61.11% focused on specific oncological types, as shown in Table II (10,17,19,20,25–27,54–90). These two tables provide additional information about each study, including its main focus, aim/purpose, study type, the type of cancer studied and key findings. Moreover, Figs. 5 and 6 depict the trends of cancer studies in terms of study types and types of cancer, respectively, across the years.

Table I.

Publications on miscellaneous types of cancer according to study type and date of publication.

First author/s, year	Study type	Main focus	Observational/interventional	Aim/purpose	Main finding	(Refs.)
Khazzaka et al, 2022	Systematic	Incidence/		Examination of the literature	Fetal metastasis occurred	(28)
	review	occurrence/		concerning placental and fetal	mainly in patients with
		risk factors		metastases among pregnant	placental metastases
				women with cancer via the	derived from melanoma
				identification of clinical and	and lung cancer primaries
				pathological characteristics,	and was associated with
				treatment trends and prognosis	a dismal prognosis
Atat et al, 2022	Literature	Anticancer	NA	Explain the importance of 3D	3D systems are currently	(29)
	review	updates		culture in representing the	used for disease modeling
				tumor microenvironment as	and pre-clinical drug
				well as the effects of 3D	testing
				cancer cells on the behavior,
				resistance, proliferation and
				metastasis of cancer
Sacca et al, 2022	Cross-	Qualitative	Observational	Evaluation of patient trust	The role of confidence in	(30)
	sectional			predictors when seeking	seeking cancer-related
				cancer-related information	information consistently
				from doctors and the internet	influences the levels of
					trust attributed to each
					source of information
Karam et al, 2021	In vitro	MOA	NA	Evaluation of the targeted	Supports the use of	(31)
	animal			effect of parthenolide in vitro	parthenolide and urges
				and in animals, after extensive	further clinical
				experiments targeting its anti-	development
				inflammatory and anticancer
				properties
Hoteit et al, 2021	Literature	Anticancer	NA	Explain the immune-based	Immunotherapy used	(32)
	review	updates		mechanisms used in tumor	alone or in combination
				cell proliferation and	with various types of
				maintenance, as well as the	therapeutics has potential
				rationale behind various	in cancer treatment
				treatment methods
Jaafar et al, 2021	In vitro	Safety	NA	Collection of ambient	Three major sources were	(33)
				particle-bound polycyclic	found to contribute to PAH
				aromatic hydrocarbons (PAH)	emissions at the urban
				in three Lebanese coastal	background site, namely,
				cities and investigation of	traffic (48%), diesel
				their cancer risk	generators (23%), and
					incineration (29%). The
					cancer risk was found
					higher than what was
					measured at the same
					site in previous years
					with an increase of 35%
Chaftari et al, 2021	Cross-	Mortality	Observational	Use of C-reactive protein,	A simple new scoring	(34)
	sectional			procalcitonin and lactate	system for mortality
				biomarkers of sepsis to	prediction, based on
				create a prediction model	readily available clinical
				for short-term mortality	and laboratory data,
				in patients with cancer and	including procalcitonin,
				suspected infection	C-reactive protein and
					lactate was developed
					that can be used in
					emergency departments
					for patients with cancer
					and suspected infection
Massoud et al, 2021	Cross-	Qualitative/	Observational	Evaluation of the healthy	Communication gaps	(35)
	sectional	opinion		lifestyle practices recommended	between hematologists/
				by hematologists/oncologists	oncologists and patients
				for patients during treatment.	with cancer should be
				Correlational analysis between	addressed, and solutions
				the hematologists/oncologists’	to identified barriers
				sociodemographics and the	should be implemented
				lifestyle recommendations	to achieve higher quality
				they provided to patients	patient-centered care
Alrubai et al, 2022	Cross-	Qualitative/	Observational	Assessment of the	Findings including the	(36)
	sectional	opinion		psychological health status,	association between the
				depression, anxiety and stress	development of new pain
				levels of patients with cancer	and depression, raised
				in Iraq during the COVID-19	concerns regarding the
				pandemic, and the relationship	psychological health of
				between such factors and	patients diagnosed with
				sociodemographic characteristics	cancer during the
					COVID-19 pandemic
Khaled et al, 2021	Cross-	Validation	Observational	Validation of the EPIC	EPIC FFQ can be	(37)
	sectional			FFQ in Lebanon	considered a valid tool
					for the assessment of
					diet in epidemiological
					studies among Lebanese
					adults
Al-Koussa et al, 2020	Literature	MOA	NA	Discussion of different	De novo arginine	(38)
	review			arginine deprivation agents	synthesis is not
				and their mechanism of	sufficient to
				action, stressing the	compensate for the
				factors that affect cell	high nutritional
				migration and the effect of	requirements of cancer
				arginine on metastases via	cells, forcing them to
				polyamines	rely on an extracellular
					supply of arginine
Diab et al, 2020	Literature	MOA	NA	Explain the roles of CDK7	CDK7 is uniquely	(39)
	review			in cancer cells and provide	involved in the
				an overview of the	transcription regulation
				pharmacophores of CDK7	and cell cycle progression
				inhibitors, their efficacy in	in many types of cancer.
				various cancer models and	CDK7 inhibitors have
				clinical development	demonstrated a
					promising profile of
					safety with lowgrade
					side effects, and
					regimens against
					various advanced solid
					tumors are in place
					to assess their clinical
					efficacy as a single agent
					and in combination.
Bechnak et al, 2020	In vitro	MOA	NA	Study of the cytotoxicity	A375 cells treated with	(40)
				of curcumin-based colloidal	the curcumin colloidal
				nanocapsules and investigation	nanocapsules showed a
				of whether anticancer activity	significant increase in
				is enhanced by curcumin	single- and/or double-
				encapsulation	strand DNA breaks upon
					exposure to light, indicating
					promising biological effects
Hrusak et al, 2020	Cross-	Incidence/	Observational	Investigation of COVID-19	Children receiving anticancer	(41)
	sectional	occurrence/		incidence and severity among	chemotherapy may have a
		risk factors		children on anticancer	mild or asymptomatic
				treatment through a survey	course of COVID-19.
				distributed virtually over 25	While the risk of
				countries	developing a more severe
					course of COVID-19
					should not be underestimated,
					the intensity of preventive
					measures should not cause
					delays or obstructions to
					oncological treatment
Nassour et al, 2020	Systematic	Anti-cancer	NA	Systematic review of	Significant heterogeneity	(42)
	review	updates/		anticancer drugs in the	within methodologies
		waste		aquatic environment	made it challenging to
					compare results and draw
					conclusions. Nevertheless,
					the study aids the
					evaluation of proposed
					recommendations to
					guide future studies
					and reviews
Mehanna et al, 2020	In vitro	MOA	NA	Optimization and validation	The method was	(43)
				of a facile liquid	advantageous compared
				chromatography-tandem	with prototypical
				mass spectrometry method	inductively coupled
				to detect and quantify three	plasma-mass
				Ru(II) polypyridyl	spectrometry-based
				complexes in cells, plasma	techniques in vitro
				and urine	and in vivo, which
					anticipates its utilization
					in cellular uptake,
					pharmacokinetics and
					pharmacodynamics studies
Assi et al, 2020	Literature	MOA	NA	Discussion of the major	Collaborative efforts at	(44)
	review			resistance patterns and	the molecular level are
				outcomes associated with	advancing the design
				the use of prior targeted	of improved drugs or
				therapies in two oncological	combinatorial strategies
				solid tumors	and the development
					of more sensitive assays
					to monitor responses
					and resistance
El Baba et al, 2020	Literature	MOA	NA	Evaluation of how Rho	The Rho GTPases are	(45)
	review			GTPases regulate VEGF	among the most important
				signaling and the outcomes	molecules for signal
				of this interaction on the	transduction in cancer
				progression of cancer	cells. They regulate
					cytoskeleton remodeling,
					proliferation, and migration
					among others. VEGF
					controls angiogenesis and
					vascular permeability of
					endothelial cells and acts
					downstream of Rho
					GTPase-related signaling.
					The role of Rho GTPases,
					in the regulation of
					angiogenesis by modulating
					the expression of VEGF or
					regulating tube formation has
					been well established
Elias et al, 2019	In vitro	MOA	NA	Isolation of Cedrus libani	7-HC possesses promising	(18)
				extract 7-HC and investigation	anticancer and anti-
				of its anticancer and	inflammatory activities,
				antiinflammatory activities	and may serve as a lead
					molecule in cancer therapy
Doumit et al, 2019	Cross	Qualitative/	Observational	Exploration of spirituality	As the first study in the	(46)
	sectional	opinion		and its positive effect on	Middle East to address
				the family caregivers of	the meaning of spirituality
				children with cancer in	in this population, may
				Lebanon	pave the way for a
					customized palliative care
					program and integrative
					approach to patient care
Bar-Sela et al, 2019	Cross	Qualitative/	Observational	Study of the barriers	Despite relatively high	(47)
	sectional	opinion		to staff providing spiritual	levels of spiritual care
				care to patients, based on the	provision, there is a
				observation that decreased	gap between desirability
				usage of aggressive treatments	and actual provision due
				at the end of life occurs	to certain barriers, such
				when patients feel	as inadequate training
				spiritually supported. Analyzed	of healthcare professionals
				a subgroup of physicians and	and lack of space for
				nurses whose inclination to	appropriate discussions
				provide improved spiritual
				care provision was unrealized
Hageh et al, 2018	In vitro	MOA	NA	Investigation of a series	The photocytotoxicity of	(48)
				of sterically encumbered	these long-lived cuprous
				Cu(I) bis-phenanthroline	phenanthroline complexes
				complexes for use in PCT	was successfully
					demonstrated, suggesting
					that this class of
					photosensitizers may be
					exploited for PCT
					applications
Moghnieh et al, 2017	Literature	Guidelines/	NA	Provide guidelines on the	Various factors play a role	(49)
	review	updates		management of infections	in the management of
				in patients with febrile	febrile neutropenia in
				neutropenia in an era of	patients with cancer,
				rising antimicrobial	including local
				resistance, devised by	microbiology epidemiology
				panel members on behalf	and the availability of
				of the Lebanese Society	diagnostic tests and
				of Infectious Diseases	antimicrobial agents
				and Clinical Microbiology.
				These are expected to
				support care providers by
				providing standardized
				care processes
Doumit and	Cross-	Qualitative/	Observational	Investigation of the	The enabling factors were	(50)
Khoury, 2017	sectional	opinion		factors facilitating and	social/family support;
				hindering the coping	talking about it; strong
				methods of Lebanese	religious beliefs; and the
				parents of a child with	communication style
				cancer	of health workers. On
					the other hand, the
					deterring factors were
					the waiting time and the
					hospital stay; changes in
					the couple's relationship;
					and sibling rivalry. Nursing
					and medical staff need
					to be conscious of parents’
					coping strategies and their
					impact on family dynamics
					and the relationship between
					the family and the health
					care team.
Razik et al, 2017	In vitro/	MOA	NA	Synthesis of two series	Certain pyrazolopyrimidine	(51)
	animal			of new purine bioisosteres	derivatives possessed
				comprising a pyrazol	in vitro anti-inflammatory
				(3,4-d)pyrimidine scaffold	and anticancer activities
				linked to piperazine moiety
				through different amide
				linkages and evaluation
				of their anticancer activity
Liu et al, 2021	Literature	MOA	NA	Review of the roles of	Demonstrates the	(52)
	review			divalent metal ions in	importanceof substrate-
				the inhibition of IDH,	metal ion complexes
				their role in the	in R132H IDH1
				tricarboxylic acid cycle	catalysis and the basis
				and the associated	for selective
				metabolism	R132H IDH1 inhibition
Bar-Sela et al, 2019	Cross-	Qualitative/	Observational	Survey of physicians and	Development level	(53)
	sectional	opinion		surgeons from the Middle	of a country is a key
				East to investigate the	factor influencing attitudes
				linkage between attitudes	toward spiritual care and
				to spiritual care and the	its actual provision
				spiritual care of patients
				with cancer
Assi et al, 2020	Cross	Qualitative/	Observational	Assessment of whether	NGS combined with	(44)
	sectional	opinion		molecular profiling helps	IHC/other tests provides
				physicians in therapeutic	useful information for
				decision making via the	aiding the treatment
				analysis of molecular	decisions of oncologists
				profiles of cancer after	in routine clinical practice
				the failure of at least
				one standard-of-care
				treatment using NGS, IHC
				and other tests

3D, 3-dimensional; NA, not applicable; MOA, mechanism of action; COVID, coronavirus disease; EPIC FFQ, European Prospective Investigation into Cancer Food Frequency Questionnaire; VEGF, vascular endothelial growth factor; 7-HC, 7-himachalen-7-ol; PCT, photochemotherapy; IDH, isocitrate dehydrogenase; NGS, next-generation sequencing; IHC, immunohistochemistry.

Table II.

Publications on specific cancer types according to study type and date of publication.

Study	Cancer type	Study type	Main focus	Observational/interventional	Aim/purpose	Main finding	(Refs.)
Jayaraj et al, 2020	Prostate	Systematic	MOA	NA	Systematic review and	The expression of	(25)
		review/			meta-analysis of the	specific miRNAs
		meta-analysis			theragnostic effects of	as theragnostic
					miRNA and the utility	biomarkers in
					of miRNAs as clinical	medical oncology
					theragnostic biomarkers	was suggested
Khalife et al, 2020	Breast	Literature	MOA	NA	Review of miRNAs	Specific miRNAs	(26)
		review			involved in BC,	were shown to be
					highlighting their effect	up- or downregulated
					on drug and therapy	in BC
					resistance
Elias-Rizk et al, 2020	Breast	Cross-	MOA	Observational	Evaluation of various	LncRNA H19 could	(27)
		sectional			lncRNA H19 threshold	be a potential
					levels in normal vs.	marker for BC
					proliferative and malignant	diagnosis, prognosis
					tissues, and investigation	and risk management
					of the link between such
					levels and BC classification
Chemaly et al, 2022	Gastric	Systematic	Incidence/	NA	Comparative analysis of	Gastroesophageal	(54)
		review	occurrence/		data on gastroesophageal	cancers after gastric
			risk factor		cancer occurrence after	bypass procedures
					gastric bypass procedures	occur commonly in
						the excluded
						stomach where
						many are not
						identified by
						conventional means
Assouad et al, 2022	Kidney	Cross-	Incidence	Observational	Analysis of kidney cancer	Lebanon presented	(55)
		sectional			occurrence in Lebanon over	an average-to-high
					12 years and a comparative	ASR for kidney
					analysis with other countries	cancer compared
						with other countries
						in its region, but a
						below-average ASR
						compared with
						countries worldwide
Swayden et al, 2021	Colorectal	In vitro	MOA	NA	Testing the therapeutic	Colon cancer cells	(56)
					potential of targeting	are partially
					colon cancer cells	auxotrophic for
					via arginine deprivation	arginine and
					induced by HuArgI(Co)-	sensitive to
					PEG5000	HuArgI(Co)-
						PEG5000-induced
						arginine deprivation
						Activation of
						autophagy is not
						protective, but
						induces cytotoxicity
						and leads to cell
						death
Nader et al, 2021	Breast	Case report	Safety	Observational	Description of a case of	Early recognition	(57)
					immune-mediated	of the side effects
					encaphalitis and a	and their treatment
					literature review of the	is crucial
					neurological immune-
					related adverse events
					associated with various
					checkpoint inhibitors
Chatila et al, 2021	Colorectal	Cross-	Incidence/	Observational	Demographical description	Lebanese patients	(10)
		sectional	occurrence/		of Lebanese patients with	affected by CRC
			demographics		CRC. The method of	tend to present with
					detection, age of onset,	advanced disease
					stage at presentation,	stages, leading to
					treatment modalities and	poor prognosis and
					survival rate are detailed	survival
El-Mais et al, 2021	Pancreatic	In vitro	MOA	NA	Examination of the	HuArgI (Co)-PEG5000	(58)
					effects of arginine depletion	shows promising
					induced by HuArgI(Co)-	results for arginine
					PEG5000 on PANC-1 cell	depletion in the
					migration, adhesion and	treatment of pancreatic
					invasion	cancer cells
El-Saghir et al, 2021	Breast	Literature	Qualitative/	NA	Explorative commentary	Genetic counseling,	(17)
		review	opinion		presenting the challenges	continuing education,
					of oncologists in the	infrastructure, testing,
					diagnosis and management	expertise and
					of BC with BRCA gene	financial support
					mutations in Lebanon and	are required to
					the Middle East	fulfill unmet needs
						in the management
						of BRCA mutation
						carriers
Khater and Abou-	CNS	Literature	Anticancer	NA	Elaboration of the	Potential mechanisms	(59)
Antoun, 2021		review	updates		interventions that may	include the
					contribute to the clinical	overexpression and
					therapeutic resistance	activation of
					observed in pediatric	compensatory
					CNS tumors during	tumorigenic
					medical trials of c-Met	mechanisms within
					targeting agents	the tumors or
						ineffective drug
						delivery methods
Atallah et al, 2021	Ovarian	Cross-	Incidence/	Observational	Testing the rate, repartition	Serous histology,	(60)
		sectional	occurrence/		and risk factors of lymph	grade 3 tumors,
			risk factors		node metastasis in patients	positive peritoneal
					with epithelial ovarian	cytology, advanced
					cancer	clinical stage,
						interval surgery and
						bilateral adnexal
						involvement predict
						lymph node
						metastasis in
						patients with
						epithelial ovarian
						cancer
El-Chami et al, 2021	Breast	In vitro	MOA	NA	Evaluation of the effect	LeTx treatment	(61)
					of LeTx on the migration,	reduced the
					adhesion and invasion of	migration, adhesion
					BC cells, and its potential	and invasion of BC
					mechanism involving the	cells, and this effect
					dysregulation of the Rho	was associated with
					GTPases RhoA and Cdc42	the dysregulation of
						RhoA and Cdc42
Hilal et al, 2021	Colorectal	Cross	Survival	Observational	Comparative study of	In younger patients	(62)
		sectional			rectal cancer tumor	a worse disease-
					characteristics and outcomes	free survival and
					in patients older or younger	evidence of an
					than 40 years in a Lebanese	association between
					institution	younger age at
						diagnosis and poor
						outcomes was
						observed, suggesting
						that the personalized
						upfront intensification
						of treatment should
						be considered in the
						young
Jaafar et al, 2021	Prostate	In vitro	MAO	NA	Evaluation of the role of	StarD13 acts as a	(63)
					StarD13 and how it targets	tumor suppressor
					and interacts with cancer	that inhibits the
					molecules	invasion of PCa cells
Fayad et al, 2021	Lung and	In vitro	MAO	NA	Investigation of the	Complex C3 was	(64)
	breast				photochemistry and	observed to be a
					effect of four strained	promising selective
					photoactivatable	photoactivatable
					polypyridyl ruthenium(II)	chemotherapeutic
					complexes on A549 NSCLC	agent that induces
					and MDA-MB-231 triple	reactive oxygen
					negative BC cells	species production
						and apoptosis
Bahmad et al, 2021	CNS	In vitro	MOA	NA	Testing the potential	Tideglusib targeted	(19)
					antitumor effect of	neuroblastoma CSCs,
					tideglusib on three	thereby overcoming
					human neuroblastoma cell	therapy resistance
					lines, SK-N-SH, SH-SY5Y
					and IMR-32
Khalil and Abi-	Pancreatic	In vitro	MOA	NA	Evaluation of the	Pancreatic cancer	(65)
Habib, 2020					sensitivity of pancreatic	cells are auxotrophic
					cancer cells to HuArgI(Co)-	for arginine and
					PEG5000-induced arginine	sensitive to
					deprivation and the	HuArgI(Co)-
					mechanisms underlying	PEG5000-induced
					deprivation-induced cell	arginine deprivation
					death
Idriss et al, 2020	Breast	In vitro	MOA	NA	Investigation of the	Vitamin E family	(66)
					antiproliferative effects	member β-T3 is as
					and pro-apoptotic	a promising
					mechanisms of β-T3 on	anticancer agent
					the human breast	that is more
					adenocarcinoma cell lines	effective than
					MDA-MB-231 and MCF7	γ-T3 for the
						treatment of human
						BC
Nasreddine et al, 2020	Ovarian	In vitro	MOA	NA	Assessment of arginine	Activation of	(67)
					auxotrophy in ovarian	autophagy following
					cancer cells through the	arginine-deprivation,
					induction of arginine	is not protective
					deprivation by HuArgI(Co)-	and mediates cell
					PEG5000	cytotoxicity leading
						to death by autophagy
Bahmad et al, 2020	CNS	Literature	Anticancer	NA	Summary of drug	Drug repurposing	(68)
		review	updates		repurposing methodologies	or repositioning is
					adopted to cure pediatric	a promising approach
					brain tumors and	for the identification
					discussion of compilation	of novel therapeutic
					approaches that may elevate	strategies to target
					drug repurposing to an	brain tumors and
					advanced level	overcome therapy
						resistance
Tfayli et al, 2020	Lung	Randomized	Treatment	Interventional	Assessment of the benefits	The addition of	(20)
		controlled			of immune checkpoint	immunotherapy to
					inhibitors in the	chemotherapy did
					neoadjuvant therapy of	not appear to
					patients with early-stage	enhance the overall
					NSCLC	response rate in
						patients with
						resectable NSCLC
						in the neoadjuvant
						setting as the study
						failed to meet its
						primary endpoint
Joumaa et al, 2020	Colorectal	In vitro/	MOA	NA	Testing the effect of	Chamomile acts as	(69)
		animal			aqueous chamomile	a potent dietary
					extract against DMH-	chemopreventive
					induced CRC in mice	agent against
						DMH-induced CRC
Tannous et al, 2020	Leukemia	In vitro	MOA	NA	Investigation of the	ENL exerts promising	(70)
					potential anticancer effect	anticancer effects on
					of the flaxseed lignans	AML cell lines in vitro,
					secoisolariciresinol	by promoting DNA
					diglucoside, enterodiol and	fragmentation and the
					ENL on AML cells	intrinsic apoptotic
					in vitro and the underlying	pathway, highlighting
					molecular mechanism	the protective health
						benefits of flax
						seeds in leukemia
Younes et al, 2020	Breast	In vitro	MOA	NA	Evaluation of the potential	AELE exhibits a	(71)
					anticancer activity of	selective
					AELE in vitro in MDA-	antiproliferative
					MB-231 and MCF-7 BC	and pro-apoptotic
					cell lines, and	effect on chemo-
					determination of the	resistant MDA-
					toxicity level in normal	MB-231 BC cells,
					mesenchymal stem cells	providing evidence
						for the antitumor
						effects of A. cherimola
Ghali et al, 2019	Breast	Case-	Incidence/	Observational	Exploration of the	Reveals the positive	(72)
		control	occurrence/		contribution of NF-κB	association of
			risk factors		variants to the pathogenesis	rs3774937 with BC
					of BC in a Middle Eastern-
					North African population
Bahmad et al, 2019	CNS	Literature	MOA	NA	Summary of the key	Experimental	(73)
		review			molecules in neuroblastoma	evidence from
					CSCs	neuroblastoma cell
						lines, patient-
						derived xenografts
						and primary tumors
						is presented
Al-Koussa et al, 2019	Colorectal	In vitro	MOA	NA	Testing the cytotoxic effect	Arginine depletion	(74)
					of HuArgI(Co)-PEG5000	is a potential selective
					on the CRC cell lines HT-29,	approach for inhibiting
					Caco-2 and Sw837	the motility and
						invasion of CRC cells
Henaine et al, 2019	Colorectal	Cohort	Anticancer	Observational	Evaluation of the clinical	Targeted therapy	(75)
			treatment		effectiveness of targeted	associated with
					therapy in patients with	standard therapy is
					metastatic CRC in	highly prevalent in
					Lebanese oncologic units	Lebanon in
					and an estimation of the	metastatic disease
					costs	and the associated
						medical cost is
						substantial
Cianci et al, 2019	Ovarian	Systematic	Incidence/	NA	Review of evidence	Sarcopenia appears	(76)
		review	occurrence/		describing the association	to have an important
			risk factors		of sarcopenia with	role in the
					surgical and oncological	oncological outcomes
					outcomes in patients with	of patients with
					ovarian cancer	ovarian cancer
Najem et al, 2019	Colorectal	In vitro	MOA	NA	Evaluation of the effect	Profound	(77)
					of SAHA, a pan-histone	antitumorigenic effects
					deacetylase inhibitor	of sequentially
					and/or DAC, a DNA	combined SAHA and
					methyltransferase inhibitor,	DAC were found in
					on the Caco-2 human colon	the CRC cell line
					cancer cell line in vitro	and new insights
						into the
						corresponding
						molecular mechanism
						were obtained
El-Amm and	Prostate	Literature	Anticancer	NA	Reviews the pivotal	Apalutamide and	(78)
Aragon-Ching, 2019		review	updates		clinical trials that	enzalutamide are
					supported the approval	new anti-androgen
					of apalutamide and	treatment options
					enzalutamide in the	in the nmCRPC
					non-nmCRPC setting	setting
					as well as the main
					potential and challenges
					of these agents
Hoter et al, or 2019	Prostate	Literature	MOA	NA	Reviews the functions	HSPs may have a	(79)
		review			and role of HSPs in	role in PCa
					PCa progression	progression and it
						is necessary to
						further evaluate
						the approach of
						HSP inhibition
						as a cancer
						treatment strategy
Al Saud et al, 2018	Breast	Systematic	Safety	NA	Explanation of the	Zoster reactivation	(80)
		review			flap sensory	in breast reconstructed
					reinnervation mechanism	patients objectively
					of the reconstructed breast	demonstrates
					based on clinical findings,	reinnervation of the
					and provision of a	skin flap
					diagnostic and management
					algorithm for zosteriform
					rash in patients with breast
					cancer
Bedoui et al, 2018	Colorectal	Case-	Incidence/	Observational	Investigation of the	IL-17A rs10484879	(81)
		control	occurrence/		association of six	single nucleotide
			risk factors		IL-17A gene variants	polymorphism and
					(rs3819024, rs2275913,	IL-17A haplotypes
					rs3819025, rs10484879,	AGGTG and GAGTG
					rs7747909 and rs3748067)	constitute independent
					with CRC susceptibility in	factors for CRC
					a Tunisian population	susceptibility. IL-17A
						may be a target for
						future CRC
						immunotherapy
Ghali et al, 2018	Breast	Case-	Incidence/	Observational	Evaluation of the	ESR1 alleles and	(82)
		control	occurrence/		relationships among	genotypes, and
			risk factors		estrogen receptor	specific 3-locus
					ESR1 and ESR2 variants,	ESR1 haplotypes
					breast cancer and	are associated with
					associated features in	increased breast
					Tunisian women	cancer susceptibility
						in Tunisian women
						However, the ESR2
						variant and specific
						1-locus ESR1
						haplotype have a
						protective effect
Al Hassan et al, 2018	CNS	In vitro	MOA	NA	Investigation of the	Metformin	(83)
					anti-invasive	demonstrates anti-
					antimetastatic effect	invasive antimetastatic
					of metformin on	potential. There was a
					glioblastoma multiforme	significant decrease
					and its mechanism of	in the survival of
					action	SF268 cancer cells
						in response to
						treatment with
						metformin. Furthermore,
						metformin's efficiency
						in inhibiting 2D cell
						motility and cell invasion
						in addition to
						increasing cellular
						adhesion was also
						demonstrated in
						SF268 and U87 cells
Nader et al, 2018	Prostate	Literature	Anti-cancer	NA	Provision of a	Promising results in	(84)
		review	updates		historical summary and	locally advanced PCa
					explanation of the	and high-risk PCa
					contemporary use of	have been obtained
					chemotherapeutic agents	in the neoadjuvant
					in PCa in various states	and adjuvant settings
					and phases of the disease
Daaboul et al, 2017	Colorectal	In vitro/	MOA	NA	Investigation of the	Low dose HC	(85)
		animal			anticancer activity of	treatment induced
					Daucus carota oil extract	cell cycle arrest and
					HC against SW1116 colon	promoted apoptosis
					cancer cell lines, and	via inhibition of the
					evaluation its effect in a	MAPK/ERK and
					DMH-induced colon	PI3K/AKT pathways.
					carcinogenesis model in	HC treatment
					black 6 mice	exerted an antitumor
						effect in vivo with
						no significant toxicity
						to the mice
Abou-	CNS	Literature	Anti-cancer	NA	Review of the progress	CSC-targeting	(86)
Antoun et al, 2017		review	updates		in CSC biology and its	approaches in
					association with targeted	combination with
					therapies that may	current clinical
					clearly differ between	therapies have the
					pediatric and adult	potential to be
					brain tumors	more effective owing
						to their ability to
						compromise CSC
						maintenance
Najar et al, 2017	Breast	In vitro	MOA	NA	Investigation of the role	MSCs strongly	(87)
					of bone marrow-derived	contribute to the
					MSCs in the mediation	adaptation and
					of selective bone	invasiveness of
					metastasis by BC cells	BC cells in skeletal
						tissues
Salem et al, 2017	Breast	Cross-	Diagnosis	Observational	Analysis of the breast	Breast density	(88)
		sectional			mammogram density	distribution in
					distribution in	Lebanon is similar
					Lebanese women and	to that in western
					its correlation with BC	society. Also, similar
					incidence	to other studies, it
						showed that high
						breast density is
						statistically associated
						with BC, particularly
						in older and
						menopausal women
El-Amm et al, 2017	Prostate	Literature	Anticancer	NA	Examination of the	Abiraterone has shown	(89)
		review	updates		companion PROs in	benefits in the second-
					conjunction with	and first-line (post-
					abiraterone acetate	and pre-chemotherapy)
					use, as PROs are	settings, with
					increasingly considered	improvements in
					as a key metric for drug	overall survival
					label claims when	and secondary end
					regulatory agencies	points such as PSA
					grant approval	and radiographic
						response rates, time
						to PSA progression
						and progression-free
						survival
Shebaby et al, 2017	Skin	In vitro/	MOA	NA	Examination of the	The F2 fraction	(90)
		animal			cytotoxic effect of	exhibited marked
					Daucus carota oil	antitumor activity
					fractions on human	against DMBA/
					epidermal keratinocytes	TPA-induced skin
					and the chemopreventive	carcinogenesis, possibly
					activity of the pentane	mediated through
					diethyl ether fraction on	inhibition of the
					DMBA/TPA-induced	MAPK/ERK and
					skin carcinogenesis	PI3K/AKT pathways
					in mice

NA, not applicable; ASR, age-standardized rate; MOA, mechanism of action; HuArgI (Co)-PEG5000, pegylated cobalt-substituted recombinant human arginase I; CRC, colorectal cancer; BC, breast cancer; CNS, central nervous system; LeTx, anthrax lethal toxin; PCa, prostate cancer; NSCLC, non-small cell lung cancer; CSCs, cancer stem cells; T3, tocotrioenol; miRNA, microRNA; DMH, 1,2-dimethyl hydrazine; ENL, enterolactone; AML, acute myeloid leukemia; lncRNA long non-coding RNA; AELE, Annona cherimola ethanolic leaf extract; SAHA, suberoylanilide hydroxamic acid; DAC, decitabine; nmCRPC, metastatic castration-resistant PCa; HSP, heat shock protein; IL, interleukin; HC, β-2-himachalen-6-ol; MSCs, mesenchymal stromal cells; PROs, patient-related outcomes; PSA, prostate-specific antigen; DMBA, dimethylbenzanthracene; TPA, tetradecanoylphorbol acetate.

Figure 5.

Cancer study types at the Lebanese American University between 2017 and 2022.

Figure 6.

Different types of cancer studied at the Lebanese American University between 2017 and 2022.

6. Principal findings

The aim of the present investigation was to assess the quantity and quality of cancer studies reported by the LAU and explore their respective objectives and areas of focus. The review encompasses in vitro, in vivo and animal studies. A relatively high number of literature reviews and a prevalence of observational studies over experimental ones were conducted. This finding may be expected since observational studies are generally easier to perform, more convenient and less stringent compared with interventional studies, although they carry a lower level of evidence (91).

The aims of the included studies varied, and in some cases it appeared that the main objective was solely descriptive. Therefore, it is essential to conduct more interventional, experimental and well-controlled human studies that possess higher external validity and generalizability. Such studies would lead to more definitive conclusions and trustworthy recommendations (92).

The present analysis reveals that researchers at the LAU who are interested in cancer have focused on a variety of research areas. The most common type of study involved laboratory experiments, namely in vitro studies, which accounted for more than one-third of the LAU studies. Animal models are important tools in cancer research in vitro and in vivo, as they can be used in the identification of carcinogens, development of cancer therapies and drug screening, and for providing insights into the molecular mechanisms of tumor growth and metastasis (93). In addition, they are easy to manipulate, homogenous, accessible and do not require human participants (94). The latter point was highlighted in the present study, which showed that this type of study was most prevalent during 2020-2021, during the era of COVID-19.

Special updates and reviews on novel anticancer therapies were also shown to be prevalent in the present study. Notably, these findings, particularly those concerning the regulatory roles of small RNAs, have provided new insights to improve the global understanding of cancer biology. Although these types of studies were the most prevalent during the year 2020, prior to the spread of COVID-19 and the economic crisis that impacted research funding negatively in Lebanon, in coming years, broader revelations about fundamental aspects of cellular biology are likely to increase our understanding of the aberrant behavior of cancer cells and notably contribute to the advancement of biomedical research (14). In addition to anticancer treatment, other studies had additional objectives, such as determining the incidence and prevalence of specific types of cancer, identifying risk factors associated with certain cancers and exploring their socio-economic and psychological impacts. Indeed, the diverse range of findings from these studies on cancer underscores the broad spectrum of interest of researchers to this field and emphasizes the requirement for well-balanced, patient-centric research strategies that can yield improved outcomes and higher cure rates (95).

Just a few decades ago, clinical investigators and physicians were often advised to refrain from engaging in oncology due to its complexity and the discouraging clinical outcomes it yielded. Additionally, conducting cancer research required significant financial investment and relied on patients dedicating their time and effort (96). Currently, the primary challenge lies in the development of fundamental research on cancer prevention and treatment to impede the occurrence of new cases and reduce the global incidence of cancer.

Although the annual output of cancer research appears to be low when compared with that of other publications on different research subjects, a sharp increase in the number of cancer publications was noticed during the years of 2018 and 2019 in the present study. This underlines the increased involvement of LAU scholars in research as the aim of expanding the number of publications and citations, as well as the support offered by the academic institution as an incentive, seems to have had a positive impact on the publication rate of papers on cancer. In fact, Boutros and Fakih (97) argued in their recent publication that the number of academic publications was associated with academic promotion across all institutional settings. The authors also concluded that the positive consequences of the number of publications of each faculty member suggests that this factor should be a priority for administrators to consider when making decisions regarding promotion. LAU is a leading private and nonsectarian higher education institution that operates under a charter from the Board of Regents of the University of the State of New York, and has a large publication volume relative to its faculty size, which makes it an ideal source of relevant information (98). In terms of quality, LAU provides incentives for researchers to publish their studies in the top 10% of international journals; thus, LAU is a research-active institution of higher learning in Lebanon and the region, with no compromise in its commitment to quality teaching (99). Moreover, the urgency of conducting cancer research has escalated due to the high prevalence of cancer worldwide, with approximately one in two individuals receiving a cancer diagnosis in their lifetime (100). Despite current treatments, cancer-associated mortality and morbidity rates remain high (6). This global situation mirrors the situation in Lebanon, as indicated by the 2021 report from the Global Cancer Observatory of the National Cancer Registry, which revealed an increase in cancer cases despite ongoing research on cancer (22). As a result, oncological research has garnered public funding and global monetary investments to incentivize clinical investigators to pursue cancer research (101).

Despite the aforementioned increase in cancer-associated publications, a reduction in the number of publications was observed in 2021. A possible explanation for this is the outbreak of the novel COVID-19 that has impacted all types of research in various forms (102,103). Another potential explanation is the lack of funds required for research in general imposed by the severe socio-economic Lebanese crisis and political instability manifested by unprecedented rates of unemployment, inflation and poverty, and a rapid devaluation of the Lebanese currency since the beginning of 2021 (104,105).

Research on breast and colorectal cancer was found to be the most prevalent among that on all types of cancer, accounting for >30% of all cancer studies. This finding is not unexpected since, according to previous studies, these types of cancer were the most prevalent in Lebanon during the last 5 years (22,106). Unfortunately, research on breast and colorectal cancers decreased in 2022 since Lebanon was continuing to face a serious economic crisis with an effect on fiscal and human resources.

Reflecting upon the approaches to cancer research outlined in the present study, it is necessary to highlight several further recommendations. First, it is essential to conduct more research using real-life data in order to accurately assess the actual impact of research on cancer incidence, treatment, outcomes and prevention techniques. Additionally, there is a requirement for more clinical studies involving the users and beneficiaries of cancer research, such as patients and their families. It would be beneficial for these studies to involve a greater representation of individuals from real-world populations, with the development of a prospective study plan to establish specific targets for trial enrolment based on disease epidemiology and incidence. Moreover, it is crucial to allocate more robust, sustained and predictable funding for additional clinical and translational longitudinal molecular profiling studies in large and diverse cohorts of patients with cancer. This will aid in understanding the natural progression of cancers and exploring the role of biology and genetics in cancer health disparities. Furthermore, the national public health workforce should prioritize cancer control initiatives that aim to reduce the incidence, morbidity and mortality of cancer. These initiatives may also focus on improving the quality of life for individuals with cancer by implementing evidence-based interventions for prevention, early detection, diagnosis and treatment. Additionally, it is important to develop well-planned strategies to guide future cancer research.

7. Significance of the study and future implications for policy and practice

The issue of cancer research studies being underrepresented or misrepresented is an important factor contributing to therapy delays and proactive measures are required to address this. The importance of the present review lies in its summary of the different cancer studies that were conducted in an academic university during a 5-year period. The review has shown that cancer research is an attractive topic for many academic researchers; however, the spread of COVID-19 and the economic crisis had a major impact on this type of research, which might have contributed to a shift in study types towards more observational or in vitro studies as well as a remarkable reduction in research output, particularly after the spread of COVID-19 in 2020. From this perspective, it is essential to emphasize that researchers must re-focus their efforts on conducting studies associated with cancer, since cancer research should be recognized as one of the most prevalent health concerns, as is COVID-19. To develop new therapies, gain a deeper understanding of cancer prognosis and survivorship and ensure the availability of new drugs in all healthcare settings, a collaborative effort involving the diverse cancer research community in each country is necessary. Translational cancer research, particularly interventional or experimental human studies, is recommended to be an integral part of the delivery of oncology care, ensuring that valuable knowledge is gained in academic institutions and nationally. For this reason, policy proposals should be made to enhance access to digital healthcare, expand healthcare programs, allocate funds for experimental cancer research and provide financial support to healthcare institutions. Moreover, interventional studies that focus on anticancer therapy should be the primary interest of pharmaceutical companies as well as research centers since, according to the present results, only a few of these were conducted.

It is important to emphasize that the impact of cancer research can be amplified when organizations use a multidisciplinary approach, as demonstrated by the diversity of studies in the present review, which can guide and enhance future evaluations.

8. Conclusions

At present, scientists seldom contemplate an ultimate cure for cancer. However, further research on the short-term and long-term effects of current cancer therapies is necessary. For instance, efforts can be made to address the psychological and socioeconomic challenges faced by cancer patients during their treatment, or to find methods of mitigating the potential side effects experienced during therapy. By combining technological advancements with ongoing operational research, the field of oncology will be able to move on from the era when surgery and chemotherapy were the sole treatment options available.

Funding Statement

Funding: No funding was received.

Availability of data and materials

Not applicable.

Authors' contributions

NKS wrote the literature review, was responsible for the methodology and organized the findings. ST collected and analyzed data, designed and guided the study, and drafted and critically revised the final version of the manuscript. Data authentication is not applicable. Both authors have read and confirmed the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.