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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

CR Swart Memorial Lecture: Mr Cecil le Fleur
2006-08-08

Khoe and San call for government to speed up policy dialogue with indigenous communities  

 Mr Cecil le Fleur, leader of the National Khoe-San Consultative Conference and member of the executive management of the National Khoe-San Council, has called for a national policy on indigenous peoples to protect the human rights and special needs of indigenous people in South Africa.

 Mr Le Fleur delivered the 38th CR Swart Memorial Lecture on the Khoe and San at the University of the Free State (UFS).  He commended the UFS for its serious approach to the Khoe and San and for initiating initiatives such as a research project on the Griqua in which various aspects linked to language, -culture, -history, - leadership, their role in the South African community (past and present) and the conservation of their historical cultural heritages will be covered.   

 “The policy dialogue with indigenous communities initiated by government in 1999 and supported by the International Labour Organisation (ILO), has been exceedingly slow, owing to political and bureaucratic problems,” said Mr Le Fleur.

 According to Mr Le Fleur the slow pace is also impacting negatively on the United Nations’ efforts to expand the international standards and mechanisms for human rights so as to include the special needs of indigenous peoples.

 “The successful adoption of a South African policy would probably have a major impact on the human rights culture of Africa and, more specifically, on the UN system,” he said.

 “South Africa has a powerful moral authority internationally and is willing to use this authority in multilateral forums. At this stage, however, South Africa’s Department of Foreign Affairs (DFA) may not take an official position on UN instruments and declarations pertaining to indigenous issues, until the Cabinet has resolved its own domestic policy position,” he said. 

 According to Mr le Fleur it therefore came as a great surprise when the DFA brought out a positive vote in the UN for the adoption of the "Draft Declaration on the Rights of indigenous Peoples" in June this year, even before the completion of the policy process. 

 Policy consolidation in South Africa is the primary key to creating a new policy climate in Africa in order to protect the rights of indigenous peoples.  “The existing constitution of the Republic of South Africa is one of the most liberal on the continent, and embraces the concept of redress of past discrimination.  It already includes a clause (Section 6) making provision for the protection of language rights for Khoe and San peoples - the fist peoples of southern Africa,” he said. 

 “If South Africa can effectively integrate this ‘third generation’ of collective rights within an existing democratic constitution, this will send a clear message to Africa and the world that indigenous rights are a necessary component of human and civil rights in modern democracies,” he said.

 Mr Le Fleur proposed an institutional framework based on set principles that would satisfy the needs and aspirations of the Griqua and other first indigenous peoples in South Africa.  “The proposed framework was based on the notion of vulnerability as a result of colonialism and apartheid, which stripped us of our indigenous identity, cultural identity and pride as people.  This injustice can hardly be addressed within the existing mechanisms provided by the current text of the Constitution,” he said.

 Mr Le Fleur also proposed that the principles of unique first-nation status, as recognised in international law, should be applied in the construction of the framework of the constitutional accommodation for the Khoe and San. 

 Mr Le Fleur further proposed that the Khoe and San’s indigenous status in constitutional terms must be separate from the constitutional acknowledgement of their status as a cultural community, as envisaged in sections 185 and 186 of the Constitution of 1996.

 According to Mr Le Fleur, the suggested mechanism should make provision for structures such as:

  •  A statutory representative council for First Indigenous Peoples of South Africa at a national level;
  • a separate Joint Standing Committee on Indigenous and Traditional Affairs, in both the National Assembly and the National Council of Provinces on which the Khoe and San can be represented;
  • a representative structure for the Khoe and San in the legislature of each relevant province; and
  • ex officio membership in the relevant structures of local government.

Media release
Issued by: Lacea Loader
Media Representative
Tel:   (051) 401-2584
Cell:  083 645 2454
E-mail:  loaderl.stg@mail.uovs.ac.za 
24 August 2006


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