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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

UFS Winter Graduation Ceremony
2012-06-18

UFS awards record number of master’s degrees and doctorates

The University of the Free State (UFS) celebrated an increase in postgraduate successes with a record number of master’s degrees and doctorates that were awarded during the winter graduation ceremony at the Bloemfontein campus on Thursday 14 June 2012.

A total of 481 master’s degrees and 82 doctorates were awarded in two ceremonies in the Callie Human Centre on the Bloemfontein Campus. This is the most postgraduate qualifications to be awarded at a single graduation ceremony.

DiMTEC has reason to celebrate
Dr Andries Jordaan (second from right) with some of the people who received their master's degrees. From the left are Kehinde Balogun, the couple Olive Chisola-Darris en Clement West Darris, and the couple Everson Ndlovu en Patience Sibongile Ndlovu.
Photo: Leatitia Pienaar
18 June 2012

DiMTEC had reason to celebrate at the winter graduation ceremony. The Disaster Management Training and Education Centre for Africa delivered a healthy crop of 32 master’s degrees and one doctorate.

This was the most master’s degrees that the centre has been awarded at one opportunity. The doctorate, however, was not at DiMTEC – Andries Jordaan, the director of the centre, obtained his Ph.D. in Agricultural Economy.

It was also the first time that two couples received their master’s degrees at the centre at the same time.

Speaking at the event, Dr Jordaan said former students of the centre were using their expertise worldwide. Some of them are in senior positions at the United Nations, in African countries, Afghanistan, and elsewhere. DiMTEC’s students hail from 17 African countries, including French-speaking countries.

“I am proud that we have a footprint right across Africa,” he said.

Three travel all the way from Europe for their MBAs
Smiles on an important day. From the left are: Kasina Baker, Friederike Hackelberg, and Johanna Kössler and her parents and sister.
Photo: Stephen Collett
18 June 2012
No distance, time or money could prevent three MBA graduates from Europe from attending the winter graduation ceremony in Bloemfontein. Two of them were exchange students who were so captivated by the university and the country that they undertook their MBA studies at the Business School.

Friederike Hackelberg of Bremen, Germany, was an exchange student in 2008 and extended her stay to do an MBA. Johanna Kössler of Bolzano, Italy, was also an exchange student who succumbed to the charms of the UFS and South Africa. She brought her parents, George and Nannie, and her sister, Magdalena, with her to attend the graduation ceremony.

Kasina Baker of Warsaw, Poland, began her studies while her husband was working in Kenya. She wanted to study at a quality institution and thus chose the UFS's Business School.

Jessica gets three prestigious medals
Jessica Potgieter (right) was the first student in almost three decades to receive three prestigious medals at the Winter Graduation Ceremony. She received the Dean's medal as best Master's student in the Faculty of Natural and Agricultural Sciences, the Senate Medal as best Master's student at the university and the Award for Scientific Achievement by the South African Association for the Advancement of Science. She is seen here with her mother, Mrs Ilse van Rhyn, and Dr Khotso Mokhele, Chancellor.
Photo: Johan Roux
18 June 2012
Three daughters, three degrees for proud Kovsie mom
Liezel Alsemgeest and Adri Kotzé.
Photo: Leonie Bolleurs
18 June 2012

Adri Kotzé, Faculty Manager in the Faculty of Law, is a very proud parent. In the course of one year, all three her daughters will receive degrees from the University of the Free State (UFS). First in line is the eldest, who received her Ph.D. in Business Management at the Winter Graduation Ceremony.

Liezel is a lecturer in the Department of Business Management at the UFS, where she lectures, publishes and hopes to further her research in finance. “I enjoy working at the university because you have the freedom to do your own thing and focus on whatever you like,” she says.

The title of Liezel’s thesis is Customers’ perception of business units within an agricultural business in South Africa. Her focus is on the subjects of customer satisfaction and financial management, with a specific focus on the management of agricultural businesses.

Middle sister Corné will be graduating with a master’s degree in Occupational Therapy in December, while the youngest, Adéle, will receive her B.A. in Media Studies and Journalism at the Autumn Graduation Ceremony in 2013.

“I am very proud of all three my daughters,” says Adri.
Sasolburg minister receives Dean's Medal for best master's degree in Theology
Rev. Frans Redelinghuys.
18 June 2012

Rev. Frans Redelinghuys of the Reformed Church in Sasolburg received his master’s degree in Theology at the University of the Free State’s Winter Graduation Ceremony. Rev. Redelinghuys was also awarded the Dean’s Medal as the best master’s degree student in the Faculty of Theology.

The focus of his dissertation is Spirituality. “My lecturers are all people who practice what they preach and they have shared their knowledge with me.,” he says.

“My studies also contributed to my personal development,” says Rev. Redelinghuys.

Student from the Netherlands receives degree at UFS Winter Graduation Ceremony
Deborah Van den Bosch-Heij.
Photo: Leonie Bolleurs
18 June 2012

Deborah Van den Bosch-Heij from the Netherlands was awarded a Ph.D. at the Winter Graduation Ceremony by the Faculty of Theology of the University of the Free State (UFS). Her thesis, Spirit and healing in Africa: A reformed pneumatological perspective, is an interdisciplinary investigation of the relationship between the Holy Spirit and healing in Southern Africa. The research addresses the need for a reviewed and contextually reformed approached to healing.

Deborah started her career as a minister at the Valkenburg Congregation of the Protestant Church in the Netherlands in 2001. She was appointed by the missionary department of her church to lecture at the Justo Mwale Theological University College in Lusaka, Zambia in 2005. It was here that she decided on the topic of her thesis. Prof. Rian Venter from the Department of Systematic Theology at the UFS, who is also involved at the Justo Mwale College, is Deborah’s promoter and assisted her in her studies whilst she was in the Netherlands. It was also Prof. Venter who made Deborah aware of the importance of interdisciplinary research.

Well-known judge's granddaughter receives degree

Judge Joos Hefer and Annelie de Man.
Photo: Leonie Bolleurs

Annelie de Man, a law researcher at the Supreme Court of Appeal in Bloemfontein received her master’s degree at the Winter Graduation Ceremony of the University of the Free State (UFS). She is Judge Joos Hefer’s granddaughter. Annelie was also awarded the Dean’s Medal as the best master’s degree student in the Faculty of Law.

“Today is one of the biggest highlights in my career,” says Annelie, who received exposure to the field of law from a young age.

In September, she will be leaving for Italy to study for a master’s degree in European Human Rights at the European Inter University.

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