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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

Professor launches his book, opposition parties attend
2011-03-22

Prof. Hussein Solomon
Photo: Stephen Collett

“We are good in opposing people, but we’re less good in opposing ideas.” This was how Prof. Jonathan Jansen, Vice-Chancellor and Rector of the University of the Free State (UFS) introduced the book launch of Against all Odds: Opposition Politics in Southern Africa.

The event was hosted in collaboration with the publisher under the title: Are opposition parties in South Africa in a crisis? This formed part of a series of dialogue sessions, organised by the Centre for Africa Studies, in the run up to the local elections.
 
Amongst those interested who attended the evening in the Senate Hall of the CR Swart Building on the Main Campus were various politicians, students, staff en a panel consisting of academics and the respective provincial representatives of the ANC and DA.
 
Dr Mcebisi Ndletyana from the Human Sciences Research Council (HSRC), acted as arbiter.
 
Proff. Hussein Solomon, author of Against all Odds: Opposition Politics in Southern Africa, also lecturer at the UFS, as well as Dirk Kotzé, Head of the Department of Political Science at Unisa, delivered enriching lectures on the stance and positioning of opposition parties.
 
Prof. Hussein, who spoke first, circumscribed the context of the political climate in the country, based on his book. “The problem that political science encounters is that everybody becomes experts on the internet, while they have no experience of what is happening in South Africa.” He said that when political parties in the country are under discussion, voters often allow myths and/or stereotyping to influence their concept of it. ‘’If there are no opposition parties, there is no democracy and people are deprived of their vote.”
 
Prof. Kotzé stated in his speech that it was not only opposition parties who had to make the government watch its step, but also the status that the country acquired, amongst others, from its connections, i.e. collaborative agreements such as BRICSA and the country’s inclusion in the G20. He left the audience with a question about how they were going to become involved in politics, and with his rhetoric question referred to options like social networks and movements.
 
Mr Sibongile Besani, the ANC'S secretary in the Free State, said the DA grew due to it’s swallowing of other parties; something he claims is taking the country backwards. He also described the use of personalities by opposition parties as means of association a weakness. He added that voters will continue voting for the ANC because they can associate themselves with the party’s vision.
 
In contrast, Mr Roy Jankielsohn, provincial leader of the DA, said voters and parties unite under their core vision for the country as like in the case of the ANC during the liberation struggles.
 
During the question-and-answer session, which followed after Mr Jankielson’s speech, Prof. Kwandiwe Kondlo, upon completion and summary of the discussions, stated firmly that the opposition parties are in a crisis. “The start of the solution is to recognise the problem. That is why our democracy finds itself in the state in which it is; because the opposition does not fulfil the role that they are supposed to fulfil.“ Prof. Kondlo is the head of the Centre of Africa Studies at the UFS.
 
He concluded by stating that the economic basis in the country was not transformed. “We cannot say that people determine their futures if they posses nothing. Opposition parties must start to communicate at this level in order to table something new. Our democracy must become more inclusive at political and material level.”

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