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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

Situation on the Bloemfontein Campus, and letter to parents
2016-02-28

Letter to parents from Prof Jonathan Jansen, Vice-Chancellor and Rector of the UFS 

 

Statement by Prof Jonathan Jansen, Vice-Chancellor and Rector of the University of the Free State (UFS) about the situation on the Bloemfontein Campus


1.    As all of you know, last night we witnessed a really tragic event at Xerox Shimla Park on the Bloemfontein Campus on the occasion of the Varsity Cup rugby match between NMMU (FNB Madibaz) and UFS (FNB Shimlas).
2.    The game started at 18:30 and about 17 minutes into the match, a group of protestors sitting on the north-eastern side of the stadium decided to invade the pitch and disrupt the game in progress.
3.    After a short while, some of the spectators also invaded the field, chasing and brutally beating those protestors whom they caught.
4.    As a university leadership we condemn in the strongest terms possible the vicious attack on the protestors. Nobody, repeat nobody, has the right to take the law into their own hands. While the protests were illegal and disruptive, it did not harm to the physical well-being of the spectators.
5.    The reaction from the group of spectators, however, not only opened old wounds, it trampled, literally and figuratively, on the dignity and humanity of other human beings. This we condemn in no uncertain terms, and no stone will be left unturned to find those who acted so violently on what should have been a beautiful occasion that also brought families and young children together to enjoy an evening of sport.
6.    I cannot over-emphasise our level of disgust and dismay at the behaviour of the spectators. It is NOT what the University of the Free State (UFS) is about and we are working around the clock to gather evidence on the basis of which we will pursue both charges and, in the case of students, also disciplinary action on campus.
7.    At the same time, the invasion of the pitch is also completely unacceptable and we will seek evidence on the basis of which we will act against those who decided to disrupt an official university event.
8.    Clashes between students occurred afterwards on campus and members of the Public Order Policing had to disperse some of them. The situation was stabilised in the early hours of the morning.
9.    Disruption continued this morning (23 February 2016) when students damaged some university buildings, a statue, and broke windows. Additional reinforcements from the South African Police Service were brought in to stabilise the campus. Additional security has also been deployed.


Broader picture
10.    We are very aware of the national crisis on university campuses and the instability currently underway. While the UFS has been largely peaceful, we have not been spared this turmoil, as last night’s events showed.
11.    We are also conscious of the fact that even as we speak, various political formations are vying for position inside the turmoil in this important election year. In fact, part of the difficulty of resolving competing demands is that they come from different political quarters, and change all the time.
12.    We are therefore learning from reliable sources that the Varsity Cup competition is, in fact, a target of national protests in front of a television audience.
13.    And we are aware of the fact that these protests are not only led by students but also by people from outside who have no association with the university. Just as the violent spectators involved on Monday night also included people from outside the university.

The demands

14.    My team has worked around the clock to try to meet the demands of contract workers demanding to be in-sourced. In fact, this weekend past, senior colleagues sat with worker leaders in the township to try to find ways of meeting their demands. We were hoping that such an agreement would be finalised by Monday afternoon (22 February 2016), but on the same Monday morning workers and students were arrested after moving onto Nelson Mandela Avenue, after which the South African Police Service (SAPS) took over as the matter became a public safety concern outside the hands of the university. Since then, it was difficult to return the workers to settle on a possible agreement.
15.    The fact is that the UFS has been in constant negotiation with contract workers to provide our colleagues with a decent wage and certain benefits. In fact, towards the end of last year we raised the minimum wage from R2 500 to R5 000. We were in fact hoping that the continued negotiations would improve that level of compensation even as we looked at a possible plan for insourcing in the future. We made it clear that if we could insource immediately, we would, but that the financial risk to the university was so great that it threatened the jobs of all our staff. Those negotiations were going well, until recently, when without notice the workers broke away and decided to protest on and around campus.
16.    While these negotiations were going on, the Student Representative Council (SRC) on Monday 22 February 2016 also decided to protest. While the vast majority of our 32 000 students were in classes and determined to get an education, a very small group led by the SRC President decided to protest; some invaded the UFS Sasol Library and the computer centre, and with the President eventually made their way to Xerox Shimla Park on which route they confronted the police, interrupted traffic and in fact injured some of our security staff as well as police officials.
17.    The university is definitely proceeding to collect evidence on these illegal and violent acts and will also act firmly against students involved in these protests.

Summary
18.    The events of Monday night represent a major setback for the transformation process at the UFS. While we have made major progress in recent years—from residence integration to a more inclusive language policy to a core curriculum to very successful ‘leadership for change’ interventions for student leaders—we still have a long way to go.
19.    One violent incident on a rugby field and we again see the long road ahead yet to be travelled. As I have often said before, you cannot deeply transform a century-old university and its community overnight. We acknowledge the progress but also the still long and difficult path ahead. We will not give up.
20.    We have 32 000 students on our campuses; the overwhelming majority of them are decent and committed to building bridges over old divides as we have seen over and over again. So many of our students, black and white, have become close and even intimate friends working hard to make this a better campus and ours a better community and country. Like all of us, they are gutted by what they saw on Monday, but the hundreds of messages I received from parents, students, and alumni this past 20 hours or so said one thing—keep on keeping on. And we will.

 

The Big Read: An assault on transformation (Times Live kolom deur Prof Jonathan Jansen: 25 Februarie 2016)

 

 

 


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