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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

MBA Programme - Question And Answer Sheet - 27 May 2004
2004-05-27

1. WHAT MUST THE UNIVERSITY OF THE FREE STATE (UFS) DO TO GET FULL ACCREDITATION FOR THE MBA PROGRAMMES?

According to the Council on Higher Education’s (CHE) evaluation, the three MBA programmes of the UFS clearly and significantly contribute to students’ knowledge and skills, are relevant for the workplace, are appropriately resourced and have an appropriate internal and external programme environment. These programmes are the MBA General, the MBA in Health Care Management and the MBA in Entrepreneurship.

What the Council on Higher Education did find, was a few technical and administrative issues that need to be addressed.

This is why the three MBA programmes of the UFS received conditional accreditation – which in itself is a major achievement for the UFS’s School of Management, which was only four years old at the time of the evaluation.

The following breakdown gives one a sense of the mostly administrative nature of the conditions that have to be met before full accreditation is granted by the CHE:

a. A formal forum of stakeholders: The UFS is required to establish a more structured, inclusive process of review of its MBA programmes. This is an administrative formality already in process.

b. A work allocation model: According to the CHE this is required to regulate the workload of the teaching staff, particularly as student numbers grow, rather than via standard management processes as currently done.

c. Contractual agreements with part-time staff: The UFS is required to enter into formal agreements with part-time and contractual staff as all agreements are currently done on an informal and claim-basis. This is an administrative formality already in process.

d. A formal curriculum committee: According to the CHE, the School of Management had realised the need for a structure – other than the current Faculty Board - where all MBA lecturers can deliberate on the MBA programmes, and serve as a channel for faculty input, consultation and decision-making.

e. A system of external moderators: This need was already identified by the UFS and the system is to be implemented as early as July 2004.

f. A compulsory research component: The UFS is required to introduce a research component which will include the development of research skills for the business environment. The UFS management identified this need and has approved such a component - it is to take effect from January 2005. This is an insufficient element lacking in virtually all MBA programmes in South Africa.

g. Support programmes for learners having problems with numeracy: The UFS identified this as a need for academic support among some learners and has already developed such a programme which will be implemented from January 2005.

The majority of these conditions have been satisfied already and few remaining steps will take effect soon. It is for this reason that the UFS is confident that its three MBA programmes will soon receive full accreditation.

2. WHAT ACCREDITATION DOES THE UFS HAVE FOR ITS MBA PROGRAMME?

The UFS’s School of Management received conditional accreditation for its three MBA programmes.

Two levels of accreditation are awarded to tertiary institutions for their MBA programmes, namely full accreditation and conditional accreditation. When a programme does not comply with the minimum requirements regarding a small number of criteria, conditional accreditation is given. This can be rectified during the short or medium term.

3. IS THERE ANYTHING WRONG WITH THE ACADEMIC CORE OF THE UFS’s MBA PROGRAMMES?

No. The UFS is proud of its three MBA programmes’ reputation in the market and the positive feedback it receives from graduandi and their employers.

The MBA programmes of the UFS meet most of the minimum requirements of the evaluation process.

In particular, the key element of ‘teaching and learning’, which relates to the curriculum and content of the MBA programmes, is beyond question. In other words, the core of what is being taught in our MBA programmes is sound.

4. IS THE UFS’s MBA A WORTHWHILE QUALIFICATION?

Yes. Earlier this year, the School of Management – young as it is - was rated by employers as the best smaller business school in South Africa. This was based on a survey conducted by the Professional Management Review and reported in the Sunday Times Business Times, of 25 January 2004.

The UFS is committed to maintaining these high standards of quality, not only through compliance with the requirements of the CHE, but also through implementing its own quality assurance measures.

Another way in which we benchmark the quality of our MBA programmes is through the partnerships we have formed with institutions such as the DePaul University in Chicago and Kansas State University, both in the US, as well as the Robert Schuman University in France.

For this reason the UFS appreciates and supports the work of the CHE and welcomes its specific findings regarding the three MBA programmes.

It is understandable that the MBA review has caused some nervousness – not least among current MBA students throughout the country.

However, one principle that the UFS management is committed to is this: preparing all our students for a world of challenge and change. Without any doubt the MBA programme of the UFS is a solid preparation.

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