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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

Questions about racial integration in residences answered
2007-07-31

Answers to frequently asked questions about the racial integration of student residences at the UFS

1. Why does the UFS want to change the current situation in the student residences?

There are many reasons why a new approach to placement in the student residences is necessary. However, the main reason is of an educational nature. As a university, the UFS should create an environment in its residences where students can learn to appreciate and respect the rich diversity that is on offer at the university. A university accommodates students from many different backgrounds in terms of race, language, religion, economic status, culture and other aspects. If a student can learn to appreciate the value in this rich diversity at university, he or she will also be able to appreciate the value of this diversity in the workplace and broader society.

The current situation of predominantly white and predominantly black residences has not been able to cultivate such an appreciation for diversity and respect for one another as human beings, and will not equip students with the knowledge and skills required to manage diversity.

Besides this, there are many other areas of life in the residences that need attention. For one, we need to urgently establish a human rights culture in the residences so that the rights of all students can be respected. We need to address the abuse of alcohol, provide disabled students with their rightful place, and last but not least, really entrench a culture of learning in student residences.

Let us make the residences places we can be proud of – places of learning, of diversity, of respect; places of growth and development. This is the ideal we should all strive to achieve.  

2. Why does the management want to force us to integrate?

It is a false argument to debate the issue in terms of “force”. Any decision by a University, or any other organisation, regarding matters of policy, rules and regulations implies a restriction on the choice of an individual and an obligation to comply.  What we should focus on is whether this decision of the Council is in the best interests of our students.

The management of the university believes that it has a responsibility to give students the best education possible, not only in terms of what you learn in the lecture rooms, but especially in the residences as well. The residences can be very powerful places of learning about matters of great importance, both academic and non-academic.

The parallel-medium language policy separates students into largely white/Afrikaans and black/English classes. Efforts are being made to bridge this divide in the classroom, but we can also try to eliminate it in the residences.

The university is committed to building a new culture for the entire institution that is based on values and principles – such as an academic culture, non-racialism, respect for human rights and diversity – among staff and students.

In the context of student residences, the application of these values and principles still allows substantial room for the voluntary exercising of choice by individuals as well as by Residence Committees, notably with regard to the placement of students (they can still place 50 percent of first-year students), as well as the determination of the future character and traditions of a diverse residence.

Furthermore, students can still choose their residences (subject to availability of places), can choose a roommate, and so forth.

3. What about freedom of association?

The rights we enjoy in a democracy must be balanced against other rights, as well as the laws of the country. This means that the right to freedom of association must be balanced against laws that make it illegal to discriminate against other people on the basis of race, language or religion, for instance.

Freedom of association pertains to the right of individuals to form voluntary organisations such as clubs or private boarding houses, or their right to join or not join existing organisations.  You exercise that right when you decide to become a student of the UFS, and again when you choose to live in one of its residences.

However, once you have decided to join an organisation voluntarily, you cannot subsequently demand that that organisation should provide a “club” or residence to your liking where, for instance, you only associate with your choice of co-members. You must accept the policies of that organisation.

In any case, how would that right of yours be balanced against the right of another individual who wishes to associate with a different set of co-members? (For instance – what about the freedom of a student to associate with students NOT from his own background, but indeed from another language, cultural, racial or economic background?) 

The constitutional right to freedom of association can, in any case, not be used to exclude or discriminate on the basis of race or religion (Section 18 of the Bill of Rights).

Besides, the new policy guidelines will still make provision for freedom of association. This right can be exercised freely within a diverse residence with regard to friendships, joint academic work, socialising, sport, etc.

4. Will residences not lose their traditions?

The University appreciates that there are many valuable elements of tradition in residences. However, we must bear in mind that the traditions and character of student residences have evolved and changed over time, and they will continue to evolve and to change. In addition, we do not need to accept all aspects of residence life purely on the basis of tradition, including the unacceptably high level of alcohol abuse and unsavoury, humiliating and discriminatory orientation practices. The new approach to integrated residences provides the opportunity to retain the positive aspects of the current traditions and character, but also to develop new traditions and give residences a new character.

We can now establish a tradition and a character for each residence that are reconcilable with the values of the University as a place of scholarship and are aligned with the human rights approach of our country’s Constitution, the laws of our country and the strengths and diversity of the students in a particular residence.

5. Have students been involved in this process? Is there a role for them to play after the decision has been taken by the Council of the UFS?

In the first semester of 2007, during two rounds of consultations, the primes, SRC and student organisations were consulted about the proposed new placement policy to increase diversity in residences. Some residences also made written submissions on the matter (such as Madelief, Soetdoring, Wag-'n-bietjie, Vergeet-my-nie, Emily Hobhouse). Other residences requested and were granted more time, but did not make any submissions in the end (such as Reitz and Armentum).

Management also had several meetings with the above-mentioned structures to hear first-hand from students their concerns and solutions regarding possible challenges presented by integration in residences.

During these interactions, several excellent ideas and proposals were put forward by students. These views had a definite impact on the eventual proposal that was taken to the University Council, in particular regarding the minimum level of diversity (30%) in junior residences and the fact that residences still want to have a say in the placement of students, rather than the placement decision being left in the hands of Management alone (hence the 50% placement portion of residences). Management values the effort that was put into the process by the primes and residence committees, and thanks them for their contributions.

However, it should be stressed that consultation should not be understood as a process of negotiation, nor does it imply that consensus must be reached. What it means is that Management must take a considered decision after hearing the views of stakeholders.

Management would like students to continue to provide input and ideas regarding the implementation details of the policy guidelines. Task teams have been established and students will be informed about how they can interact with the task teams on an ongoing basis.

6. But integration in the residences was tried in the past (in the late 1990s), and then it failed. Why will it work now?

Yes, the University of the Free State did integrate its residences as far back as 1993, and for a few years it worked. The UFS did it at that time and is now doing so again, because it is the right thing to do. Yet it is important to understand why the previous attempt at racial integration in residences was not successful.

Firstly, both black and white students were much polarised because of the apartheid past. Secondly, there was insufficient management support for students in the residences, the student leaders generally as well as residence heads, in terms of dealing with diversity and related issues. Thirdly, the institutional culture of the UFS and the residences in particular was not addressed as part of broader transformation and integration in residences, whereas it is now being addressed.

In addition, the current decision to integrate residences has the benefit of being implemented after several more years of integration in schooling, sport, workplaces and other aspects of life.

This decision is also based on Management’s commitment to give all the possible support it can to this process.

This is a very important initiative that the UFS is undertaking. Management, in co-operation with students, must ensure that it succeeds. Integrated residences that produce high-quality graduates equipped to deal with the challenges of the workplace and our society is a worthwhile ideal we should all strive to achieve.

If you would like to make a proposal regarding the implementation and practical aspects of the new policy, please send it to the following email address: rector@ufs.ac.za

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