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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

SRC Inauguration speech: 22 January 2005
2005-01-22

Campus Head (Prof Peter Mbati). Dean of Students (Dr Natie Luyt). Deputy Director: Student Affairs and my boss (Mr. Teboho Manchu), Members of the University executive and Academic staff members, SRC members, Leaders of trade Unions and Student organizations, Distinguished guests, Ladies and gentlemen, most importantly first entering students and Parents receive my heartfelt revolutionary greetings.

Let me extend my word of appreciation to our distinguished guests for adding value and dignity to this event. Your presence here means a lot to us. Program Director what I bring here with me, assisted by facts, and is therefore just the work of my imagination. Like a love letter addressed to a sweetheart miles away, even though you do not know how she feels, what she wants to hear, and do not even know how her face looks like.

To me a speech is just an honest and intimate conversation. That is why I got into the habit of establishing a dialogue, or a debate, with my acquaintances looking at their faces and trying to persuade them of what I am telling them.

Mr. Speaker and Madam Deputy Speaker of the Student Parliament we are gathering at this ceremony, significantly few weeks after the release of grade 12 results, with the exception of those from Mpumalanga because of fraud. The Grade 12 results also show that only 18% of Black learners matriculated with exemptions, as compared to 53, 6% of white learners. This is an indication that our education system needs an overhaul.

We are also gathered here significantly a day after the management retreat held in Bloemfontein, Masselspoort. The retreat discussed, among other things, the transformation agenda, and some possible solutions to challenges we are facing now.

Most regrettably, we are gathered here when the whole world morns the victims of Tsunami tragedy. Let me therefore tore the line and convey our deepest condolences, from the last robot of my heart, to the affected families. Our hearts and thoughts will always be occupied by this horrified tragedy.

Creating a new Institution

I would submit, for purposes of debate and discussions that this Institution should strive to specialize and excel in regional rural development studies. Since our higher education, institutions in South Africa are generally weak in rural development studies. Instead, most of them tend to have an urban orientation to their programmes. Training everybody for the cities, big business and the private sector. This is a big weakness in a country with such large rural areas and population trapped in poverty, disease and ignorance.

Women’s studies

Program Director, it is only a moron who can argue against the fact that for us to reposition the institution around the regional development challenge, we need to start first with women empowerment. It is a fact that in most of our poor communities and families, it is women who withstand the worst of poverty. They are the ones who daily have to wipe tears from children who are hungry. It is women who look after the sick, the elderly, those dying from AIDS and the jobless. They are the one who have to fetch water, make fire and cook. There can therefore be no rural development studies without women studies, in particular on how to empower them and assist in the provision of basic services, so that they are relieved from some of the burdensome task of the society.

Registration Process

Mr. Speaker and Madam Deputy Speaker of the Student Parliament let me indicate that the registration is a process and not an event, so it cannot be concluded overnight. This huge process demands for people to stay calm, as there is no crisis. People should stop being excited. At the same time, no organization should use its cheap popularity and unilaterally disrupt the continuous and smooth running of the registration process at hand.

Let me strongly indicate, madam deputy speaker, that I am on record for stating that I have forgiven all those who have wronged us. I harbour no bitterness towards the protagonists of our painful and unfortunate events of the past week. And we will overcome this process not by our own devices but by the help of Almighty God and the grace of our Lord Jesus Christ.

Concerning registration of first years, we have programs, concerning that of senior students, we have programs, regarding graduations we have programs, and concerning HIV\AIDS we have programs. So, there is no need for people to press panicking buttons.

Mr. Speaker and Madam Deputy Speaker of the Student Parliament let me be opportunistic and welcome the entire student body on Campus for the academic year 2005. May our lovely first entering students have a happy and momentous year as part of Qwaqwa Campus of University of the Free State. May your studies be fruitful and enjoyable.

Student years are generally the happiest years of your life, so please make the most of them. While you are doing, all your preparations bear in mind that University is not an opportunity, it is just creating opportunities for a person.

On behalf of SRC members, our people, our students and management members I would like to welcome you all. Even though your parents are far away, here at Uniqwa you have more brothers, more sisters and more parents. Since we will love you with the same love as if we are from one family, and I have no doubts that management members will love and care for you as if you are their own children. Should you encounter any problem while studying at the Qwaqwa Campus of University of the Free State do not hesitate to contact us at the SRC offices because we need to ameliorate any factor influencing you negatively while on campus. I wish you well in the attainment of your academic pursuit.

Senior Students: We are not faced with just a new year but another academic year where we all have to work together to achieve our common goal of building our Institution through the development of human power. I urge you to invest your whole selves in this SRC.

For quite some time now, a debate has been ranging as to, whether has there been any progress in this incorporation process, or we are just moving with no direction. This debate is important, but I hasten to add not essential. The SRC is also involved in this debate, but with definite shift in emphasis. For us it is not important to participate in the debate than it is in finding solutions for the challenges of this new chapter in the history of humankind.

To my colleagues: Comrades, we are leading this Institution with a sense of pride and duty, and I know very well that we lead men and women, students who are determined to ensure that we all reach our destination safely and on time.

I said in one of our meetings that there are more enemies on our way, more than we can imagine. I think you witnessed that during the course of this week. The excitement and unnecessary confusions caused by some confused and loosed charlatans bear testimony to my statements. We should not reveal our game plans unless we are ready to slam.

Let me also borrow from the words of the late Albert Lethuli when he said and I quote: “There remains before us the building of the new land, from the ruins of the old narrow groups, a synthesis of the rich cultural strains which we have inherited. The task is immense”. Lastly, a navy divided within its ranks will be vanquished and destroyed by the enemy, but a navy united in purpose and action, loyalty and commitment will not drawn but sail on to victory.

In conclusion, let me call upon all political structures, church denominations, developmental structures, clubs, societies and forums to put aside all their differences, ideological insinuations and forge unity towards transforming Qwaqwa Campus of University of the Free State into an institution that is seen playing vigilant role in developing students academically, politically, socially, spiritually, religiously, culturally and otherwise.

Program Director, let me end my speech by indicating that every drop of my blood is telling me that Uniqwa is my home. I firstly became a student here, I became an activist here, I became a leader here, I became a president here, I will become a graduant here and hopefully I will become an employee here. So never, doubt my commitment towards the community of this campus.

Please be informed, in a central University of Technology’s way, that if there is no UNIQWA in HEAVEN, then I am not GOING.

Let us broaden the social base.

Tello Titus Wa-Motloung President General

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