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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

Position statement: Recent reporting in newspapers
2014-10-03

 

You may have read reports in two Afrikaans newspapers, regarding recent events at the University of the Free State (UFS). Sadly, those reports are inaccurate, one-sided, exaggerated and based not on facts, but on rumour, gossip and unusually personal attacks on members of the university management.

Anyone who spends 10 minutes on our Bloemfontein Campus would wonder what the so-called ‘crisis’ is about.

We are left with no choice other than to consider legal action, as well as the intervention of the South African Press Ombudsman, among other steps, to protect the good name of the institution and the reputation of its staff. No journalist has the right to launch personal and damaging attacks on a university and its personnel, whatever his or her motives, without being fair and factual. In this respect, the newspapers have a case to answer.

But here are the facts in relation to the reports:

  1. No staff member, whether junior or senior, is ever suspended without hard evidence in hand. Such actions are rare, and when done, are preceded by careful reviews of our Human Resource Policies, labour legislation and both internal and external legal advice. Then, and only then, is a suspension affected. A suspension, moreover, does not mean you are guilty and is a precautionary action to allow for the disciplinary investigation and process to be conducted, especially where there is a serious case to answer.
  2. At no stage was the Registrar instructed to leave the university; this is patently false and yet reported as fact. We specifically responded to the media that the Registrar does outstanding work for the university and that it is our intention for him to remain as our Registrar through the end of his contract in 2016.
  3. The Rector does not make decisions by himself. Senior persons, from the position of Dean, upwards, are appointed by statutory and other senior committees of the university and finally approved by Council. No rector can override the decision of a senior committee, and this has not happened at the UFS even in cases where the Rector serves as Chair of that committee. The impression of heavy-handed management at the top insults all our committee structures, including the Institutional Forum – the widest and most inclusive of stakeholder bodies at a university – which reports directly to Council on fairness and compliance of selection processes.
  4. In the case of senior appointments, Council makes the final decision. Council fully supports the actions taken on senior appointments, including a recent senior suspension. The fact that one Council member resigns just before the end of his term, whatever the real reason for this action, does not deter from the fact that the full Council in its last sitting approved the major staffing decisions brought before it. The image therefore that the two newspapers try to create of great turmoil and distress at the university, is completely unfounded.

Even if we wanted to, the university obviously cannot provide details about staffing decisions, especially disciplinary actions in process, since the rights of individuals should be protected in terms of the Human Resource Policies and procedures of the UFS. But that does not give any newspaper the right to speculate or state as fact that which is based on rumour or gossip, or to slander senior personnel of the university. For these reasons, we have been forced to seek legal remedy and correction as a matter of urgency.

Make no mistake, underlying much of the criticism of the university has been a distress about transformation at the UFS; in particular, the perception is created that white colleagues are losing their jobs. The evidence points in the opposite direction. Our progress with equity has been slow and we lag far behind most of the former white universities; that is a fact. More than 90% of our professors are white; most of our senior appointments at professorial level and as heads of department are still overwhelmingly white. Reasonable South Africans would agree that our transformation still has a long way to go and only the mean-spirited would contend otherwise. But based on the two Afrikaans newspaper reports, an impression is left of the aggressive rooting out of white colleagues.

In the past few years the academic standard of the university has significantly improved. We now have the highest academic pass rates in years, in part because we raised the academic standards for admission four years ago. We now have the highest rate of research publications, and among the highest national publication rate of scholarly books, in the history of the UFS. We have one of the most stable financial situations of any university in South Africa, with a strong balance sheet and growing financial reserves way beyond what we had before. We now attract top professors from around the country and other parts of the world, and we have the highest number of rated researchers, through the National Research Foundation, than ever before. And after the constant turmoil of a number of years ago, we now have one of the most stable campuses in South Africa. Those are the facts.

The UFS is also regarded around the world as a university that has become a model of transformation and reconciliation in the student body. The elections of our Student Representative Council are only the most visible example of how far we have come in our leadership diversity. Not a week goes by in which other universities, nationally and abroad, do not come to Kovsies to consult with us on how they can learn from us and deepen their own transformations, especially among students.

Rather than focus on what more than one senior journalist, in reference to the article in Rapport of 21 September 2014, rightly called ‘a hatchet job’ on persons and the university, here are the objective findings of a recent survey of UFS stakeholders: 92% endorse our values; 77% agree with our transformation; 78% believe we are inclusive; and 78% applaud our overall reputation index.  Those are very different numbers from a few years ago when the institution was in crisis.

This is our commitment to all our stakeholders: we will continue our model of inclusive transformation which provides opportunities for study and for employment for all South Africans, including international students and colleagues. We remain committed to our parallel-medium instruction in which Afrikaans remains a language of instruction; we are in fact the only medical school in the country that offers dual education and training in both Afrikaans and English for our students - not only English. We provide bursaries and overseas study opportunities to all our students, irrespective of race. And our ‘future professors’ programme is richly diverse as we seek the academic stars of the future.

We are not perfect as a university management or community. Where we make mistakes, we acknowledge them and try to do better the next time round. But we remain steadfast in our goal of making the UFS a top world university in its academic ambitions and its human commitments.

END

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