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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

During 2011: Prestige Scholars Programme (PSP)
2011-12-01

The University has designed the Vice-Chancellor’s Prestige Scholars Programme (PSP) to promote and support the intellectual breadth and depth required of young scholars to pose questions and generate knowledge in their disciplines and hence to occupy the vanguards of contemporary intellectual enquiry. The programme specifically targets members of the academic staff who are near completion, or have newly completed, their doctoral studies.

The goal is to select no more than 100 of the most promising young scholars and to make substantial investments in their development towards becoming full professors. A tailored, intensive programme of support is designated that combines international placement working alongside leading scholars in the discipline of the prestige scholar, with intensive mentorship and support from within the university.

 Description: 2011 PSP_Thuthuka  Tags: 2011 PSP_Thuthuka

Elite young scholars on the Vice-Chancellor’s Prestige Scholars Programme generated R1,2 million in National Research Foundation Thuthuka and Blue Skies funding in 2011 alone. Dr Katinka de Wet in the Department of Sociology was awarded Blue Skies funding for her work on the Hybrid Identity of the HIV/Aids patient. Thuthuka Grant holders Drs Cilliers van den Berg, Olihile Sebolai, Dirk Opperman and Diaan van der Westhuizen work in the fields of German and Afrikaans trauma literature, microbiology, structural and evolutionary biology, and architecture, respectively. This broad disciplinary range typifies the depth and extraordinary range of scholarship present among junior academics at the UFS.


 Description: 2011 PSP_Liza Coetsee Tags: 2011 PSP_Liza Coetsee

Dr Liza Coetsee, a Y2-rated physicist, is the first of the Vice-Chancellor’s elite cohort of Prestige Scholars to submit for National Research Foundation rating. Dr Coetsee works on the latest of the Nanotechnology Surface Science systems housed in our Department of Physics. As Prestige Scholar, Dr Coetsee conducts research on phosphor solar cells. Her aim is to establish a new Phosphor Solar Cell field at the University of the Free State with Proff. Hendrik Swart and Koos Terblans. As a member of the Prestige Scholar Programme, Dr Coetsee will work in collaboration both with colleagues from the Nelson Mandela Metropolitan University and Prof. Eray Aydil from the University of Minnesota and Editor-in-Chief of the Journal of Vacuum Science & Technology.


 Description: 2011 PSP_Olihile Sebolai Tags: 2011 PSP_Olihile Sebolai

Dr Olihile Sebolai is one of the 2 Vice-Chancellor’s elite Prestige Scholars and a microbiologist. In 2011, Dr Sebolai was awarded a Thuthuka Grant for his research on the yeast pathogen Cryptococcus neoformans, the cause of life-threatening Aids-defining illnesses such as meningitis. Dr Sebolai considers how cryptococcal lipids mediate infectious processes leading to illness. An understanding of these cellular processes will offer hope for future drug development to combat the scourge of cryptococcal meningitis, annually causing the death of over half a million people in Sub-Saharan Africa. Dr Sebolai is also interested in mapping the prevalence and distribution pattern of cryptococcal meningitis in the Free State. This, in turn, will assist health authorities to manage current infections and plan appropriately for potential outbreaks. The Prestige Scholars Programme, with the assistance of the National Research Foundation, will afford Dr Sebolai the opportunity to pursue his research in laboratories in the United States and India in 2012 and 2013.


 Description: 2011 PSP_Louis Holtzhausen Tags: 2011 PSP_Louis Holtzhausen

Dr Louis Holtzhausen, member of the Vice-Chancellor’s Prestige Scholars Programme, has been named by the South African Sports Confederation and Olympic Committee (SASCOC) as team doctor for Team South Africa during the All Africa Games, the largest sports event in Africa. National teams from African countries participated in 23 sports events. As an esteemed South African academic in sports medicine Dr Holtzhausens’ participation was an extension of the work already being done under his supervision at the UFS’s Sports Performance Unit. Many of the athletes who prepared at the Unit were also part of the team. Elite athletes’ illness and injury profiles are one of Dr Holtzhausens’ research focus areas. The exposure to this group in competition was of great value in the identification and development of research niche areas.


 Description: 2011 PSP_ Chantel Swart Tags: 2011 PSP_ Chantel Swart

The South African Society for Microbiology awarded Dr Chantel Swart-Pistor, a Prestige Scholar on the Vice-Chancellor’s elite programme, the top prize for her PhD during a recent gala dinner in Cape Town. Dr Swart-Pistor accomplished a breakthrough in the field of nanotechnology with The influence of mitochondrial inhibitors on zoospore and ascospore development. Her supervisor, Prof. Lodewyk Kock and co-supervisors, Dr Carolina Pohl and Prof. Pieter van Wyk, also stressed the important collaboration with Proff. Hendrik Swart (Physics) and Pieter van Wyk (Centre for Microscopy), which made Dr Swart-Pistor’s work possible. She has presented her work in Beijing (Medichem 2011) and Philadelphia (Biotechnology-2011). She has been invited to return to China in 2012.


 Description: 2011 PSP_ Lizette Erasmus Tags: 2011 PSP_ Lizette Erasmus

Dr Lizette Erasmus, scientific chemist and one of the Vice-Chancellor’s Prestige Scholars, has just returned from a three-month-long research visit to Prof. Hans Niemantsverdriet at the Technical University of Eindhoven in The Netherlands and the University of California, Davis. Dr Erasmus specialises in heterogeneous catalysis. Her visit to Prof. Niemantsverdriet, one of the global experts in the field of surface science, served to round of existing research. In California, Dr Erasmus visited her mentor, Prof. Bruce C. Gates, as part of the objectives of the Rector’s programme for the internationalisation of young researchers. Prof. Gates, an expert in catalysis, could contribute to Dr Erasmus’ research on the characterisation of heterogeneous catalysis and catalytic reactions. In exchange, her expertise in organometallic synthesis added value to Prof. Gates’ existing research. Their continued collaboration gave availed them of the opportunity for interdisciplinary interaction between engineering (Prof. Gates’ speciality) and chemistry, and promises to contribute to increased collaboration between the two universities in future.


 Description: 2011 PSP_Dirk Opperman Tags: 2011 PSP_Dirk Opperman

Dr Dirk Opperman, specialist in structural and evolutionary biology and National Research Foundation Thuthuka Grant holder, joined the Vice-Chancellor’s Prestige Scholars Programme after his postdoctoral work at the Max Planck Institute (KOFO) in Germany. Dr Opperman is the recipient of institutional seed funding to establish a protein crystallisation unit, which in turn led to the donation in 2011 of a multi-million Rand X-ray diffractometer¬ from the University of the Western Cape to complement his existing access to international synchrotrons. Dr Opperman is spending part of 2011 at the University of Exeter (UK) to further his research into the three-dimensional structures of specific enzymes and their trajectories of evolution to specific functions.


 Description: 2011 PSP_Abiodun Ogundeji Tags: 2011 PSP_Abiodun Ogundeji

Abiodun Ogundeji is a member of the Vice-Chancellor's Prestige Scholars Programme. Abiodun's work was recently recognised when he and his co-authors received an award for the best contributed paper at the 49th annual conference of the Agricultural Economics Association of South Africa on the topic, Impact of climate change on planning and dealing with flood disasters in South Africa: A case study of Soweto on Sea. The paper was co-authored by Prof. Giel Viljoen from our Department of Agricultural Economics and Herman Booysen, as well as Gawie du T. de Villiers, Research Associates in the Department of Geography. Abiodun is currently conducting invaluable research on the quantification of the economic value of climate change impacts and the benefits and costs of adaptation in South Africa.

 

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