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04 December 2024 | Story André Damons | Photo André Damons
Breast Cancer Research 2024
The research team consist of Dr Beynon Abrahams (left), Viwe Fokazi, MMed.Sci student, and PhD student Songezo Vazi.

In an effort to better understand chemotherapeutic treatment response in triple negative breast cancer (TNBC) – known as an aggressive cancer with high recurrence and high mortality rate in breast cancer patients – researchers from the University of the Free State (UFS) developed a drug-resistant TNBC spheroid model that is physiologically more accurate in displaying the complexities involved in drug-resistance development.

Dr Beynon Abrahams, Lecturer in the Department of Basic Medical Sciences within the UFS Faculty of Health Sciences, says breast cancer remains the most frequently diagnosed cancer in women. It is also the most debilitating type of cancer responsible for the highest cancer mortality rates in women. Though various subtypes of breast cancer exist, TNBC is one that is of particular interest to his research team.

“TNBC is one of the most difficult cancer types to treat, due to lack of treatment targets. This often leads to treatment failure in TNBC patients, with drug resistance being a common occurrence, contributing to high death rates. TNBC is classified based on its lack of expression of common receptors such as the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, which are commonly expressed in other cancer subtypes.

“Characteristically, TNBC is known as an aggressive cancer with high metastatic potential (spreading of cancer), resulting in a poor prognosis for these patients. The current prescribed therapies for TNBC, entails multidrug combination systemic therapy including chemotherapeutic agents such as doxorubicin and cisplatin as adjuvant therapy. However, despite these therapeutic interventions, drug resistance is a common occurrence,” says Dr Abrahams.

The best available preclinical cell-based models should be used

For effective drug treatments to be developed for TNBC therapeutics, he continues, the best available disease models should be used to not only improve our understanding of the disease physiology and its numerous mechanisms involved in chemotherapeutic resistance development but also to provide accurate results when determining how safe and effective newly developed drugs are, before they may be considered for further development and testing on humans.

According to him, in preclinical cancer research the conventional methods employed to study disease mechanisms, drug action and drug resistance is ineffective. Firstly, the traditionally used preclinical 2-dimensional (2-D) cell culture models do not accurately recapitulate the architectural biology observed in vivo, second, the drug responses assessed in these models may provide inaccurate results and limit its translational potential, explains Dr Abrahams. Thus, more advanced cell-based models such as 3-dimensional (3-D) spheroids and organoids to name a few, should be considered as alternatives.

The UFS research team, in collaboration with the Centre of Excellence for Pharmaceutical Sciences (Pharmacen™) at the North-West University (NWU), recently took the undertaking to establish two triple negative breast cancer 3-D spheroid models, using the clinostat rotating bioreactor ClinoStar™ system, designed by CelVivo in Denmark. The project is funded by the National Research Foundation.

The ClinoStar™ system promotes the self-aggregation of single cells, and natural formation of 3-D spheroids, through slow rotation within a cell growth chamber known as an incubator. There are various techniques and methods available to develop spheroids and organoids, however the ClinoStar™ systems allow for the development of metabolically stable spheroids, over a longer period of time, as opposed to other methods. It also eliminates the sheer-stress conditions that are normally encountered when using 2-D cell culture models.

“We successfully established one chemotherapeutic-sensitive triple negative breast cancer spheroid model and one novel cisplatin-resistant triple negative breast cancer spheroid model. The chemo-sensitive TNBC spheroid model was evaluated for responsiveness against two clinically used chemotherapeutic agents, doxorubicin and cisplatin. We suggest that this model may be useful to screen novel compounds including traditionally used phytomedicinal material for anticancer activity.

“In our second model, the cisplatin-resistant TNBC spheroid model was also exposed to cisplatin and doxorubicin and demonstrated a resistant response in terms of growth and viability. We believe that this model may be useful to further explore drug resistance mechanisms and may also be used as a tool to assess the drug reversal potential of novel compounds. The value and impact of these models lies in that they may offer predictive drug responses that are closer to that observed in in vivo (animals), as opposed to 2-D cell cultures. This however needs to be assessed. We are currently in the process to fully characterise these spheroids models.”

Aim of the research

Dr Abrahams explains their research aims to merge the gap between conventionally used 2-D cell models and in vivo models, by providing a model that is physiologically more accurate in mimicking the in vivo conditions and complex pathways associated with drug resistance, which is otherwise not observed or accurately expressed in 2D models. “Although our research is preclinical and considered fundamental basic research, the translational potential of our spheroid models may provide options for exploring and testing alternative drugs that may be considered for translational research,” Dr Abrahams says.

Characterising other advanced cell-based cancer models

The team is currently in the process of further characterising the TNBC spheroid model based on protein and genetic expression profiles to elucidate potential therapeutic biomarkers for drug treatment as well as screening various phytomedicinal plants, to assess their antiproliferative and drug-resistance reversal potential. In addition, the researchers recently commenced a new research project that aims to develop a drug-resistant prostate cancer spheroid model using the Clinostar™ system with their collaborators at the NWU.

Advanced cell-based model research is still relatively ‘new’ in South Africa and Africa, compared to the global North. As a result, says Dr Abrahams, their NWU collaborators together with other stakeholders, initiated the establishment of the Society for Advanced Cell Culture Modelling for Africa (SACCMA) in 2021, which aims to develop the fields of advanced cell modelling, three-dimensional (3D) cell cultures, 3D bioprinting and stem cell research, in Africa. Our current inter-departmental  collaboration include researchers from the Pharmacology department, but we hope to build and expand our collaboration network in the near future.

News Archive

Institutional research culture a precondition for research capacity building and excellence
2004-11-16

A lecture presented by Dr. Andrew M. Kaniki at the University of the Free State Recognition Function for research excellence

16 November 2004
The Vice Chancellor, Prof. Frederick Fourie
Deputy Vice Chancellors, Deans
Awardees
Colleagues and ladies and gentlemen

It is a great pleasure to be here at the University of the Free State. I am particularly honoured to have been invited to present this lecture at the First Annual Recognition Function for Research Excellence to honour researchers who have excelled in their respective fields of expertise. I would like to sincerely thank the office of the Director of Research and Development (Professor Swanepol), and in particular Mr. Aldo Stroebel for facilitating the invitation to this celebration.

I would like to congratulate you (the UFS) for institutionalizing “celebration of research excellence”, which as I will argue in this lecture is one of the key characteristics of institutional research culture that supports research capacity building and sustains research excellence.

Allow me to also take this opportunity to congratulate the University of the Free State for clocking 100 years of existence.

Ahmed Bawa and Johan Mouton (2000) in their chapter entitled Research, in the book: Transformation in higher education: global pressures and local realities in South Africa (ed. N. Cloete et. al Pretoria: CHET. 296-333) have argued that “…the sources of productivity and competitiveness [in the knowledge society and global economy] are increasingly dependent on [quality] knowledge and information being applied to productivity”. The quality knowledge they refer to here is research output or research products and the research process, which (research) as defined by the [OECD] Frascati Manual (2002: 30) is:

“…creative work undertaken on a systematic basis in order to increase the stock of knowledge, including knowledge of man, culture and society, and the use of this stock of knowledge to devise new applications”

The South African Government has set itself the objective of transforming South Africa into a knowledge society that competes effectively in the global system. A knowledge society requires appropriate numbers of educated and skilled people to create quality new knowledge and to translate the knowledge in innovative ways. To this end a number of policies and strategies like the Human Resource Development [HRD] Strategy for South Africa, the National Plan for Higher Education (NPHE) and the South Africa’s Research and Development [R&D] Strategy, have highlighted human resource development and the concomitant scarce skills development as critical for wealth creation in the context of globalization. The key mission of the HRD Strategy for instance is:

To maximize the potential of the people of South Africa, through the acquisition of knowledge and skills, to work productively and competitively in order to achieve a rising quality of life for all, and to set in place an operational plan, together with the necessary institutional arrangements, to achieve this.

The R&D Strategy emphasizes that maximum effort must be exerted to train the necessary numbers of our people in all fields required for development, running and management of modern economies. Higher education institutions like the University of the Free State have a key role to play in this process, because whatever form or shape a university takes, it is expected to conduct research (quality research); teach (quality teaching – and good graduates); and contribute to the development of its community! Thus the NPHE states that the role of higher education in a knowledge-driven world is threefold:

Human resource development;

High-level skills training and

Production, acquisition and application of knowledge.

Quality research output or knowledge which as argued is critical in determining the degree of competitiveness of a country in the knowledge economy is dependent upon quality research (process). Both the process of producing quality research and its utilization cannot and does not happen in a vacuum. It requires an environment that facilitates the production of new knowledge, its utilization and renewal. It requires skilled persons that can produce new knowledge and facilitate the production of new skills for quality knowledge production. Such an environment or in essence a university must have the culture that supports research activity. Institution research culture (that is a conducive and enabling institutional research culture) is a precondition to research capacity building. Without an institutional research culture that facilitates the development and nurturing of new young researchers it is difficult, if not impossible for a university to effectively and efficiently generate new and more quality researchers. Institutional research culture is also necessary to sustain quality research and quality research output or research excellence. It facilitates the development and sustenance of the institutional and people capacities required to do research produce quality research and generally attain research excellence!

We do recognize that the patterns of information and knowledge seeking, and knowledge generation vary among field or disciplines. For example, we know that in the humanities knowledge workers often work individually, and not as collaboratively as do those of the sciences, they all however, require supportive environments – institutional research culture to achieve and sustain research excellence. An institution does not simply attain a supportive research culture, but as Patricia Clements (English Department, University of Alberta, Edmonton) in her presentation Growing a research culture argues, research culture has to be grown [and maintained]. It unifies all natural and engineering scientists; medical researchers, humanists, and social scientists.

I therefore am of the view that Institutional Research Culture is critical to research capacity building and research excellence. I therefore want to spend a few minutes looking at the characteristics of research culture. To be effective, institutional research culture has grown and sustained not only at the institutional level, but also at the faculty, school and departmental levels of any university.

What is Research Culture?

In the process of researching on institutional research culture I identified several characteristics. Many of these overlap in some way. I want to deal with some of these characteristics; some in a little more detail while others simply cursorily. In the process what we should be asking ourselves is the extent to which an institution, like the University of the Free State, and its faculties, individually and severally, is growing and or sustaining this culture.

Institutional Research Strategy: As a plan of action or guide for a course of action, the institutional research strategy must spell out research goals that a university wants to achieve. It must be a prescription of what the university needs to be done with respect to research. As a strategy it is neither an independent activity nor an end in itself, but a component part and operationalization of the university policy or mission. ( Related to this is the Establishment of Institutional research policies)

Includes and makes public the targets, e.g. achieve so many rated scientists and make sure that every year we have so many SAPSE publications. That way people keep an eye on research agendas of the university and nation.

The UFS is obviously on its way, having launched its own Research strategy (A Strategic framework for the development of research at the University of the Free Sate. August 2003). Note that this strategy refers specifically to the “Culture of research” Fig 1

A set of administrative practices to support and encourage research. Patricia Clements (English Department, University of Alberta, Edmonton) in her presentation Growing a research culture argues that that research activity and output within the her Faculty (Arts) were very low and, in spite of the numbers of staff, with no Associate Dean for Research in the Faculty as though they had accepted that research belonged to Medicine and Science and Engineering, and teaching, separated from inquiry, belonged to the Arts. With the change in the thinking about research and development of research culture, it became clear that there was a major role for research support in a faculty her size (now about 360 full time continuing academic staff). The faculty developed a support system for research and began to address the SSHRC issues.

Reduce the bureaucracy system and micromanagement of research! This however, also implies that there is capacity and policies and procedure to manage and guide research processes

Establishment of Intellectual Property regulations and assistance

Research ethics policy and safeguarding by research administration

Focused, applied and suitable nature of the delivery mode (an institution open to new methodologies for conducting research

Programmes suited both full and part-time study particularly at graduate level (Mainly at Faculty/school and department level, and depending on what’s manageable)

Hiring senior academics to engage in, teach on and supervise postgraduate students to facilitate exchange of and transfer ideas and most importantly mentorship especially in view of declining numbers of researchers in particular fields

Quality instruction and facilitation in learning about research processes

A high retention rate of students maintained by the supportive and challenging learning environment and the use of online facilities to support collaboration and in-class learning

Availability of research grants: and awareness of sourcing funds from external sources like the National Research Foundation; Water Research Commission; Medical Research Council, private philanthropies and others outside the country. For example an institution should be able to assess how much of the slice the available funds (NRF etc) its able acquire and possibly top slice from institutional budget.

Adequacy of the financial reward system to encourage university staff members to do research (General Celebration of achievement for research excellence and achievement. This ranges form Annual reports mention; celebratory dinner. At Alberta researchers were given lapels. I don’t know of any academic who do not feel a sense of achievement to get into print or recognised. Access to research facilities within and outside the institution

Provision of infrastructure to support university-based research (e.g. equipment, admin support, etc.) – but also awareness of publicly funded and available research facilities and equipment!

Internet connectivity and changes in the bandwidth of the internet to download articles

Subscription to related bodies by the library so that researcher can download articles

Facilities and resources to attend international conferences to keep one updated

Number of visiting professors/speakers targeting senior scholars and invite them to lunch to ask them to participate and to encourage their best graduate students to do so within the institution and across institutions

Research training seminars for research students including young academics

Participation of staff/students in delivering research papers to national and international conferences

Establishment of research groups to provide interaction frameworks to achieve critical mass of research-active staff

Facilitation for more research time: Targeting new scholars and giving them reduced teaching loads in their first year or two for the purpose of developing their research programs. For the purpose of helping new colleagues to see the shape of South African research support, personalizing it, and creating research community

Take research to the community and argue its necessity, and utility

And, finally celebrating excellence. We must recognize achievement - parties and public recognition for colleagues who achieve splendid things in their research.

In conclusion, I want to reemphasize that research culture has to be grown it does not simply exist in an institution. If it is grown it needs to be nourished, nurtured and sustained. An institution cannot simply leave on borrowed reputation and expect to remain research excellent. It is on this basis that instruments like the National Research Foundation rating system recognizes excellence within a given period of time and not necessarily for a life time! This it is believed encourages continued research excellence.

THANK YOU and best wishes

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