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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

Open letter from Prof Jonathan Jansen to all UFS students
2014-02-22

Dear Students of the University of the Free State

In the past four years there has emerged a new consensus on the three campuses of the University of the Free State (UFS) about the things that divide us – such as racism, sexism and homophobia. Students and campus leaders have worked hard to develop this new consensus in residences and in the open spaces on campus. There can be no doubt that new bonds of friendship have developed across the markers of race, ethnicity, class, religion and sexual orientation. I bear witness to these new solidarities every day on the campus.

You chose a white student to head up the transformation portfolio on the SRC. You chose a black captain to head up the university’s first team in rugby. You chose a white “prime” as head of residence to lead a predominantly black men’s residence. You chose a South African woman of Indian descent as Rag Queen and last week, a black student from Cape Town as the men’s Rag winner—choices not possible and never made before in our campus history. Many of you have intimate friends who come from different social or cultural or religious backgrounds. You learn together, share rooms together, pray together and party together. In other words, in the day to day workings of this university campus, you have demonstrated to campus, city and country that we can overcome the lingering effects of racism and other maladies in this new generation. You have helped create a university community inclusive of people of diverse religions, abilities, class and sexual orientation.

I have said this repeatedly that from time to time this new consensus will be tested – when a minority of students, and they are a small and dwindling minority, still act as if these are the days of apartheid. And when that consensus is tested as it was this week, and as it will be tested in the future, only then we will be able to assess the strength and durability of our progress in creating a new South African campus culture of human togetherness based on respect, dignity and embrace.

The real test of our leadership, including student leadership, is how we respond when our transformation drive is threatened.

Let me say this: I have absolute faith in you, as students of this great university, to stand together in your condemnation of these vile acts of violence and to move together in your determination to maintain the momentum for the Human Project of the University of the Free State. We have come too far to allow a few criminals to derail what you have built together in recent years.

There will, no doubt, be unscrupulous people on all sides of the political spectrum wanting to milk this tragedy for their own narrow purposes. There will be false information, rumours and exaggerations by those who wish to inflame a bad situation to gain mileage for their agendas. That is inevitable in a country that is still so divided.

I ask you, through all of this, to keep perspective. Two or ten or even twenty students behaving badly do not represent 30,000 students; a minority of violent and hateful persons do not represent the ideals, ambitions and commitments of the majority. At the same time, let us be realistic – anyone who thinks you can drive transformation without resistance clearly does not understand the difficult process of change.

The events of the week remind us, however, that we still have a long road to walk in deepening social and academic transformation at our university. Yes, we have invested hundreds of hours in training and mentorship; we have created new structures – such as the Institute for Reconciliation and Social Justice – to capture the energy and imagination of students driving transformation; we have created many opportunities for students to study and travel on this and other continents to enable cross-cultural learning; we have established formal and informal opportunities to dialogue about difficult issues on and off campus between students and their leaders; and we crafted new curricula to enable teaching and learning on the big questions of our times.

But this is clearly not enough, and so I have decided on the following immediate next steps:
  1. We will meet for several hours next week to think about how we can deepen the transformation of our university after this terrible incident.

  2. We will arrange a University Assembly on the events of the past week so that we speak with one voice on human wrongs and to re-commit to human rights and we will continue with open forum discussions during the months to come.

  3. We will review the entire spectrum of programmes, from orientation to residence life to the undergraduate curriculum, to determine how effective our interventions really are in reaching all students with respect to basic issues of human rights.

  4. We will review our media and communications strategy to determine how far and deep our messages on human rights travel across all sectors of the university community. In this regard it is important that the campus be blanketed on a regular basis with our condemnation of human wrongs and our commitment to human rights.

  5. We will commission the Institute for Reconciliation and Social Justice to review the events of the past week and make recommendations on how we can improve the campus environment so that all students are protected from harm inside residences, classrooms and in open spaces of the campus.

  6. We will take the questions raised during this week into the academic community and to the general staff of the university so that all personnel also engage with our own roles and responsibilities with respect to campus transformations.

  7. We undertake to make annual report-backs on transformation to all stakeholders in public forums so that students and staff and external communities can track the progress of the university on matters of human rights on campus.

I wish to thank my staff for acting firmly as soon as this tragic event came to our attention. We worked through the night to find and identify the perpetrators. We traced the two students and immediately handed them to the police. They were expelled. And throughout this process we offered counselling and support to the victim of this violent act.

The two former students were expelled and will now face justice in the criminal courts. It is hoped that in the course of time they will come to their senses and seek restoration and reconciliation with the student they so callously harmed. They are not part of the university community anymore.

That is the kind of university we are.

Jonathan D Jansen
Vice-Chancellor and Rector
University of the Free State
20 February 2014

 
Note: The use of the word ‘campus’ refers to all three campuses of the UFS, namely the Bloemfontein Campus, South Campus and Qwaqwa Campus.

 

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