Afatinib restrains K-RAS–driven lung tumorigenesis
Corresponding Author(s) : Herwig P. Moll
Journal of Unify,
Vol. 1 No. 12 (2019): The Volcanic sunsets, a world without oil, and how our hearts evolved for endurance
On the basis of clinical trials using first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), it became a doctrine that V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-RAS) mutations drive resistance to EGFR inhibition in non–small cell lung cancer (NSCLC). Conversely, we provide evidence that EGFR signaling is engaged in K-RAS–driven lung tumorigenesis in humans and in mice. Specifically, genetic mouse models revealed that deletion of Egfr quenches mutant K-RAS activity and transiently reduces tumor growth. However, EGFR inhibition initiates a rapid resistance mechanism involving non-EGFR ERBB family members. This tumor escape mechanism clarifies the disappointing outcome of first-generation TKIs and suggests high therapeutic potential of pan-ERBB inhibitors. On the basis of various experimental models including genetically engineered mouse models, patient-derived and cell line–derived xenografts, and in vitro experiments, we demonstrate that the U.S. Food and Drug Administration–approved pan-ERBB inhibitor afatinib effectively impairs K-RAS–driven lung tumorigenesis. Our data support reconsidering the use of pan-ERBB inhibition in clinical trials to treat K-RAS–mutated NSCLC.
A SCOPING REVIEW OF THE RELATIONSHIP BETWEEN ENTREPRENEURSHIP EDUCATION, ENTREPRENEURIAL CULTURE AND ENTREPRENEURIAL INTENTION AT HIGHER EDUCATIONAL INSTITUTIONS
Essam Hussain Al-Lawati1*,Umar Haiyat Abdul Kohar2,Ebi Shahrin Suleiman3
1*2,3Department of Business Administration, Azman Hashim International Business School, Universiti Teknologi Malaysia (UTM), Johor, Malaysia.
Email: , 2,
Article History: Received on 20 th April 2020, Revised on 15 th May 2020, Published on 11 th June 2020
The aim of this study to highlight the role of entrepreneurial culture in the relationship between entrepreneurship education and entrepreneurial intentions at higher education institutions as study variables. This study could play a vital role in guiding students to choose entrepreneurship as a career by encouraging them.
A scoping review method was used to identify critical evidence in the reviewed relationships between the three above mentioned variables, which are: entrepreneurship education, entrepreneurial culture, and entrepreneurial intention. By using the scoping review method, the authors analyzed articles from Scopus and Web of Science databases published from the year 2003 to 2019, in which 52 relevant articles out of 105 related published articles were identified using Mendeley software to filter these articles.
The results show that there was a significant positive relationship between entrepreneurship education, entrepreneurial culture, and entrepreneurial intention when the entrepreneurial culture was inculcated in entrepreneurship education activities at higher education institutions. This study shows that the most used theory is the Theory of Planned Behavior, in which most studies were done on the level of universities, and a significant volume of reviews have been carried out in developed countries.
Application of This study:
The cultivation of entrepreneurial competencies is heavily influenced by the prevailing culture, which is usually strengthened through education and directed by individual entrepreneurial intention along with the role of entrepreneurial culture. Hence, this could be useful for developing and economies in transition countries that might face high unemployment rates to focus on these variables in comparison to developed countries.
This study highlights and further proposes the mediation role of entrepreneurial culture in entrepreneurship education - entrepreneurial intention relationship based on the outcomes of the scoping review. Indeed, this relationship was just mentioned by words and not validated or measured comprehensively by the scholars. Hence, there is a chance for further studies in this body of knowledge.
Entrepreneurial Intention (EI), Entrepreneurship Education (EE), Entrepreneurial Culture (EC), Higher Education Institution ( HEI), Theory of Planned Behavior (TPB), Scoping Review.
According to , entrepreneurship is vital for a country’s economic development, especially in reducing the unemployment rate by focusing on the self-employment of individuals. In fact, many researchers suggested that one of the best solutions to reduce unemployment and to stimulate economic growth is through entrepreneurship, particularly to increase self-employed individuals (; ; ). In addition, proposed that business ideas and development in society are enhanced by entrepreneurship, whereby this scenario would develop entrepreneurial skills and knowledge and changed individual's mindsets by directing individual entrepreneurial intention. Ultimately, this change in individual mindsets to favor self-employed rather than being employed through the accumulation of entrepreneurial knowledge and skills evolves into developing entrepreneurial culture (EC) in educational institutions like higher education institutions (HEI)s. However, there is an inconsistency in the relationship between entrepreneurship education (EE), and entrepreneurial intention(EI) according to literature. Thus, suggested that there is a possibility of modifying and developing studies related to EI by having a mediator, a moderator, or any new interactions (.
pointed out several factors that affect EI, of which EE is one of these factors that increases EI by developing individual entrepreneurial mindsets, which leads to creative thinking. stated that EE had an aim to increase the awareness about taking entrepreneurship as a career, but this is not an indication to focus on the aspect of intention. Moreover, having courses that look at educating start-ups would help to shape individual intention. Moreover, stated that one of the essential results of EE is to develop the economic growth of the country, which will be by developing the knowledge, skills, and attitudes of the students. In which this development will lead to the establishment of more start-ups and create more jobs, which will help the economy of the country. However, according to , it is imperative to look at how a country can improve and develop EC to have the needed and better attitude towards entrepreneurship, which would lead to set policies for developing students' skills. Furthermore, having an entrepreneurship education would lead to having stable EC (). Moreover, opined that relevant policies could foster the creation of EC at HEIs and public research organizations, which will lead to high-impact entrepreneurship activities at HEIs (). Also, stated that many pieces of research are needed regarding cross-cultures to know the effect of values and cultures on intention. In this study, the attention will be given to the organizational culture, especially addressing the EC of HEIs.
Therefore, this paper reviews the studies of entrepreneurship, particularly the possible mediating role of EC in the relationship between EE and EI that was not yet measured or tested, which discovery will contribute new knowledge to the field. This paper starts with the review of literature on selected variables EE, EC, and EI, discussing it one by one as well as their relationships and research framework. It is followed by the methodology section, which highlights the method of scoping review whereby analysis was carried out on 52 articles from Scopus and Web of Science database. The result section presents the main aspects found in the study. The main points are highlighted in the conclusion section. Finally, suggestions for future research scope in the area are presented in the recommendation section.
In general, EI is defined as “the quality that leads an individual to pursue a career in self-employment or establish his or her own business ” . In addition, suggested that EI predicts entrepreneurial behavior, as it shows a proportion of action taken towards entrepreneurship by the individual. According to , the intention is considered as a planned behavior by individuals that play a significant role in the firm and business creation, as becoming an entrepreneur is involves people at the decision level. Also mentioned that it is vital to focus on social situations and behavior of entrepreneurs to maintain a robust and stable economy, particularly in developing countries. Besides, highlighted that EI is an outcome of cognitive progress in entrepreneurial development, as it motivates individuals to consider entrepreneurship as a career through the mental process. Hence, it was found that EE is one of the elements that lead to EI, whereby the latter is significantly influenced by the former.
defined EE as "developing the mindset, skillset, and practice necessary for starting new ventures, yet acknowledging the outcomes of such education are far-reaching.". suggested that considerable attention is paid towards EE as a discipline of study, where it could play a vital role in developing concepts and building theories. stated that it is vital to develop students' entrepreneurial competencies and skills, which is more of a psychologically oriented aspect through EE. These competencies are beneficial for entrepreneurs who have a business and potential entrepreneurs. Generally, EE has a positive effect on the development of entrepreneurial mindsets among students, whereby focusing on developing their knowledge, attitude, and skills lead to the development of EC . Besides, suggested that entrepreneurial thinking and approaches are motivated by EE, as it is apparent in the youth enrolling courses related to EE (. Also, expressed that the country needs vigorous development in EE development to create more entrepreneurs and reduce the unemployment rate. The delivery of EE can be conducted through education such as courses and workshops during the semester in schools and HEIs, which may encourage the generation of innovative ideas by developing the mindset, knowledge, and skills of the students .
Entrepreneurial Intention and Entrepreneurship Education Relationship
highlighted that student attitudes and behaviors might be affected by EE, whereby EE can enhance the development of new ideas and encourage EI . Table 1 indicates different aspects of relationships between EE and EI that should be taken into consideration, as highlighted by several researchers in this field. Moreover, researchers have identified four different types of relationships between EI (outcome) and EE (predictor): negative, positive, significant, and non- significant. Precisely, the finding demonstrates inconsistency in the relationship (positive or negative) between the two variables, which should be further investigated with the addition of more variables. There is a high chance that more studies will discover both negative or positive relationship between EI and EE, as reported by several researchers. Furthermore, several studies have reported exclusively on the positive relationship between EE and EI. On the other hand, there are also reports on the negative relationship between EE and EI.
Table 1: EE- EI relationships
defined EC as "a culture of entrepreneurship can be understood as norms, values, and codes of conduct that promote social acceptance and approval of entrepreneurial activities resulting in high self-employment rates which persist over time." The studies about EC are still at the nascent stage, as more studies related to the topic are required . proposed that the academic gives more attention to EC as a subject of interest in the field, as it has an impact on employment, business continuity, and growth of the economy. The country needs to encourage innovation, robust economic growth, and job creation (; ).
Furthermore, many researchers (; ) suggested that regions with high EC would encourage individuals with previous business experience to accelerate entrepreneurship activities through interaction between business owners and individuals, and formulation of encouraging policies by lawmakers. Like in the study of noted that strong EC represents in having individuals with previous experience in business, role social acceptance of entrepreneurship, and role model affect the level of entrepreneurship activity in the country. Besides, few researchers (; ) also suggested that government support plays a vital role in fostering EC at multiple levels. These findings demonstrate the importance of EC as a weak EC can be a significant barrier to entrepreneurial development in a country (). further strengthened the view by suggesting that economic development demands to have a long-term investment in entrepreneurship to create EC among youths. For example, in the case of the EU, it was pointed out by that EE is vital for the development of EC through the introduction of relevant knowledge, skills, and mindsets to students. In which, the next section would look at the relationship between EE and EC.
Entrepreneurship Education and Entrepreneurial Culture Relationship
It is essential for policymakers to focus on improving public policies and EE in regard to the unemployment of youth and EC development (;; ). In this regard, proposed that developing policies according to local business and EE may promote EC that can boost the local economic growth by fostering individual entrepreneurial mindset by increasing their entrepreneurial knowledge and business opportunities. Furthermore, EC is constructed based on EE, which function can be fitted into the existing model of EE (; ). According to , the implementation of EC at schools may be done by introducing guidelines and reshaping government policies towards implementing EC in schools.
stated that to develop an academic culture, HEIs should introduce entrepreneurial learning that helps in building and creating the culture throughout the nation. Hence, cooperation between students, non-academic staff, and academics at HEIs is crucial in the development of EC (; ; ). However, the development of impactful courses and curriculum has been particularly challenging at HEIs, which hampers the creation and cultivation of EC among students, . Therefore, it will be necessary for HEIs to develop an awareness program as initiatives in cultivating EC.
EE helps to change the mindsets and mentalities in society and fosters the creation of EC ; ). Strategic collaboration between government agencies and HEIs should focus on strengthening the policies and cultivating EC among students (; ; ;). Therefore, proposed that research universities should play a significant role in regards to promoting EC creation and growth nationwide. In line with this view, many researchers proposed that there is a need to have comprehensive and robust EE in HEIs to encourage the development of EC among the students (; ; ; ).The other aspect that would be highlighted is about the relationship between EC and EI .
Entrepreneurial Culture and Entrepreneurial Intention Relationship
supported the view by stating that EI will grow with the growing recognition of EC. Furthermore, demonstrated that EC affects EI positively by enhancing individuals to think about new ideas and starting their businesses. The view demonstrates the positive effect of EI on EC when supported with other relevant initiatives and action plans. In addition, suggested that bridging EC and EI will positively impact the economist, policymakers, and academics, which will eventually lead to self-employment. Moreover, many researchers are of the opinion that the country needs to promote EC in order to bring out the value of entrepreneurship in the educational system ().
opined that the readiness to take on entrepreneurship activities depends on the institution's entrepreneurial culture. Thus, it is essential to establish a strategic relationship between academics, students, and various divisions in university in terms of transforming and developing youth’s entrepreneurial mindsets at university. It is crucial to create ideal curricula for students and lecturers to enhance entrepreneurial thinking (). Hence, the next step is to propose the mediating role of EC between EE and EI by looking at the reviewed studies.
The mediating role of Entrepreneurial Culture between Entrepreneurship Education and Entrepreneurial Intention
opined that having low EC could negatively affect students' skills and knowledge. On the other hand, suggested that EE helps in extending EC and innovation by introducing necessary changes in students’ mindset and skills. Table 2 shows that several researchers have reported on the positive relationship between EE with EC. It was also found that the development of EC has a positive effect on individual perception and intention towards entrepreneurship, which encourages business and creation of a new venture.
Table 2: Relationship of EE - EC and EC - EI
Figure 1 elaborates on the proposed relationship between EE (IV), EC ( Mediator), and EI (DV) as per the review studies, which could be validated later. According to (; ) suggested that the mediator is considered to be the third variable, which looks at the mechanism where the dependent variable (DV) is affected by the independent variable (IV). The model gives focus to a significant relationship between the variables: IV and mediator; mediator and DV; IV and DV (; ). There is a significant positive relationship between the variables in the discussion, EE, EC, and EI; this study focuses on the role of EC as a mediator in the relationship between EE and EI. Previous studies' findings have only suggested the role of EC as a mediator in the relationship between EE and EI, but the model has yet to be validated or tested (; ). Highlighting these variables and relationships would be a contribution to the knowledge by addressing for measuring and validating later. It is proposed that EE encourage the development of EC by cultivating the right mindset and intention towards firm creation; EC, in turn, drives individual EI.
Figure 1:Proposed Research Framework
Source: Authors’ Analysis
Hence, to focus on literature mapping, Table 3 represents the number of references used in the literature review and study analysis for each variable and its relationship. The next section is about the method used to analyze related articles via scoping review, followed by sections for results and conclusion.
Table 3: Literature mapping with the number of used references
The scoping review focuses on examining the broader aspect of mapping relevant literature. In this study, it is helpful to know and identify aspects such as the main concepts, gaps, quantitative and qualitative data, time, and contexts of the research (). stated that scoping review helps researchers to study unspecific relationships for observation and consideration, prior to conducting a systematic review. Additionally, suggested that scoping review "addresses an exploratory research question aimed at mapping key concepts, types of evidence, and gaps in research related to a defined area." On the other hand, viewed scoping review as a process that "aim to map rapidly the key concepts underpinning a research area and the main sources and types of evidence available, and can be undertaken as stand-alone projects in their own right, especially where an area is complex or has not been reviewed comprehensively before." In short, researchers find scoping review as a tool to address primary research done on a specific topic or field, which allows for identification of the key concepts, theories, and contextual aspects of the research.
Figure 2: The scoping review processes
viewed scoping review as a tool to identify the gaps and connect the different aspects in research regardless of the quality of the publication, which can help researchers to identify relevant topics for future research. reported that scoping review is used the most in health-related research. There are only a few studies from non-health fields that adopted scoping review, which signifies the need to have more studies in emerging fields to adopt scoping reviews, such as entrepreneurship-related study. The process in scoping review is shown in Figure 2 as proposed by , which starts with identifying research questions and relevant studies, followed by study selection and charting data; the final part involves collecting, summarizing, and reporting the results.
Figure 3: The process of study selection
Source: Authors’ Analysis
Figure 3 illustrates the process in study selection, which involved analysis on leading search strings that include EE, EC, and EI. The search was restricted to scholarly papers published between the years 2003 and 2019. The results yielded 53 relevant documents from Scopus and 52 from Web of Science, bringing a total of 105 articles. After filtering for duplicated papers using Mendeley software, 52 related articles were recovered for analysis based on the criteria shown in Table 4. Based on the number of papers discovered, investigation on the relationship between EE, EC, and EI was identified as a new topic of interest, as more studies are needed in the area.
There were three research objectives (RO) for this study, which are first to identify the relationship between EE, EC, and EI by determining the trends in published studies. Second, to highlight the trend of studies with regards to these variables’ relationship. Last but not least, to highlight the contextual aspect, types of educational institutions, and used theory involved in these studies.
Table 4: Criteria of literature for inclusion and exclusion in scoping review
Therefore, the research questions (RQ) to be answered in this paper are as follows:
RQ1: Is there any relationship between EE, EC, and EI?
RQ2: What is the trend of studies done with regard to these variables’ relationships?
RQ3: Where do most of the studies take place in terms of contextual aspect, educational institutions, and used theory?
The search for relevant studies was conducted using Scopus and Web of Science databases, with the use of the following keywords: entrepreneurial culture, entrepreneurial intention, entrepreneurship education. The selected studies were used to find a correlation between the three variables in order to identify the relationship between the variables; the criteria of literature for inclusion and exclusion during the selection process are elaborated in Table 4. Mendeley software was used to remove duplicates of articles . The period of studies was chosen from the year 2003 until 2019. The selection demonstrates that the analyses were conducted only based on relevant scholarly papers from the past 16 years. The documents were published as scholarly journal articles and conference papers; books from the field of management were excluded. This method of scoping review has been adopted by several researchers (; ; ; ; ), where some of them considered articles published on Scopus and Web of Science databases as a sole reference.
To answer RQ1, Table A1 in the Appendix also presents the review on the number of studies conducted to examine the relationship between the three variables. These key findings are summarized as follows: (a) majority of the studies were conducted to examine the relationship between EE, EC, and EI; (b) 16 studies were conducted to examine the relationship between EE and EC; (c) the least number of studies were conducted to examine the relationship between EC and EI with only eight published studies.
Figure 4 presents the trend in the published articles according to the year of publication, which focuses on RQ2. Generally, the number of publications in this particular area of research fluctuated from year to year. The earliest studies were carried out in 2003 with two papers being published, while the latest carried out in 2019 with five published papers. However, the peak in the number of articles published is observed in the year 2015, with 13 papers, where most studies were conducted in developed countries from EU; the trend observed may be related to the efforts in EU at the time to implement policies that are capable of encouraging entrepreneurship and boosting its cultural development. It is worth to note that fewest articles were published in the years 2008, 2009, and 2012, with only one paper recorded.
Figure 4: The trend in the number of studies based on the year of publication
Source: Authors’ analysis
Figure 5: Distribution of articles according to the publisher
Source: Authors’ Analysis
Based on the analysis of the number of articles according to the publisher in Figure 5, the maximum number of papers published by a particular publisher is only two. For instance, only two articles (; ) were published in International Small Business Journal; two articles ) were published in Mediterranean Journal of Social Sciences. The rest of the journals and conferences had only one paper published.
To highlight more on RQ 3, Table 5 presents the number of published studies in these countries, based on United Nations economy classifications according to income level, which is: (a) developed economies, (b) economies in transition, and (c) developing economies. The findings show that most of the studies in this area were conducted in developed countries, which involved the published works in 23 countries of developed economies. On the other hand, there were four studies conducted in countries with economies in transition and 29 studies in 16 countries with developing economies. In developed countries, most studies were conducted in the European Union (EU) member countries such as Spain, the UK, Portugal, and Germany. The observation may be due to the great emphasis put on EE, EC, and EI as part of policies development in most EU countries and collaboration between the stakeholders, government, and educational institutions in the region. From another perspective, many developed countries face issues of the high unemployment rate, and this may lead to more studies that investigate the factors that motivate and direct youth toward entrepreneurship.
Table 5:Researches by country
Source: Compiled by authors
Additionally, most of the studies conducted focused more on samples from universities than schools. A possible explanation for the observation may be that most researchers were interested to solve the high unemployment rate among graduates from HEIs, whereby the development of entrepreneurship at HEIs is considered as one of the practical solutions. In addition, based on the analysis shown in Appendix (Table A1), it is imperative to focus on developing EC in HEIs in order to strengthen interactions between HEI and stakeholders (private and public).
The findings also demonstrate that researchers have adopted several theories in this field of study, such as Theory of Planned Behavior (TPB), Entrepreneurial Event Model (EEM), Human Capital Theory (HCT), Self-Efficacy Theory (SET), Social Cognitive Theory (SCT), Personality Trait Theory (PTT), and McClelland’s Need of Achievement Theory (N-Ach). However, the theory used the most was TPB. The finding may be explained by the fact that there is a relationship between EC, EI, and EE, which is mainly observed in educational institutions such as schools and universities. Moreover, most developed countries have strong EC compared to other regions due to policy implementation, noting that the most used theory by researchers was TPB.
Starting with research questions like RQ1, it was found that there is a significant relationship between EE-EC-EI, as most studies reported on a positive correlation between EE, EC, and EI. Besides, the mediating role of EC in the relationship between EE and EI was mentioned but not validated or tested, which suggests the need for further research in the area in the future. Moreover, RQ2 was about the trends in publication, in which the findings demonstrate that there is fluctuation in the volume of published works in this particular area of study. Interestingly, the trend peaked in the year 2015, where most studies were conducted in EU countries due to attention given toward the implementation of entrepreneurship-related policies in the member countries. On the other hand, the answer for RQ3 is observable in the findings, which show that most studies in the area were conducted in developed countries compared to countries of economies in transition and developing economies at HEIs. The findings also demonstrate that the most adopted theory by researchers studying in this field was the TPB .
It is recommended that policymakers formulate policies that aim to boost the development of EC by fostering strategic collaboration between stakeholders and educational institutions. Additionally, academic institutions are encouraged to improve EC among academic and non-academic staff, students, and the rest of stakeholders through innovative and practical approaches, such as curriculum development and entrepreneurship training seminars. In addition, practitioners (entrepreneurs) should be allowed to play a proactive role as a role model for the students, as the interaction between educational institutions and entrepreneurs will help in keeping the students abreast of the latest development in the entrepreneurial field.
For further research, it is recommended to measure and validate these relationships by having a standard and reliable instrument as there is only a handful of research carried out to study the relationship between EE, EC, and EI. This study could also be further improved by conducting a comprehensive review using other research approaches or empirical studies in the future. Besides, developing and economies in transition countries might need to have more studies in this regard. Finally, studies about the relationship of EE-EC-EI could be synergized between individual and organizational level.
Essam Hussain Al-Lawati and Dr. Umar Haiyat Abdul Kohar worked on the idea of shaping, reviewing, and developing the plan of work. Moreover, Essam Hussain Al-Lawati worked on searching, collecting, filtering articles collection, and analyzing these studies. Meanwhile, Dr. Umar Haiyat Abdul Kohar and Dr. Ebi Shahrin Suleiman were supervising and guiding Essam Hussain Al-Lawati throughout the process and supporting the research process.
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Table A1: The analysis of relationships between variables, educational institutions, and theories adopted.