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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

Prof Jonathan Jansen bids farewell to Kovsies
2016-08-31

 

Dear Kovsie staff and students

This is my final message to you all.

I wish to use this opportunity for some brief reflections, share a word of gratitude, and convey a sense of the future for our beloved university.

Since the announcement of my departure, I have had more than a dozen breakfasts with mainly students, but also staff, to offer an opportunity for the final sharing of thoughts and, of course, goodbyes. The most common questions asked at those breakfast sessions were the following, with my responses. I repeat them here, since these might also be of interest or concern to you.

What are your proudest achievements?
Two things. The increase in the academic standard for the UFS, both in terms of admission standards and pass rates, but also in relation to the requirements for appointment and promotion especially of professors. This is important because in a globally competitive world, a university stands or falls by the quality of its degrees. And for this you need the best students and the best professors.

What would you do differently, given another chance?
Nothing. I believe that leadership is about doing the best you can with the cards you are dealt in the circumstances in which you are placed. There is no point in second-guessing past decisions. I have always been ambitious as a leader, knowing that most of my goals would be met, and that some would not. That is normal in large and complex organisations, and so, I do not sit around pondering regrets, only remembering with gratitude the things we could achieve together.

What did you learn?
A lot. I learnt that our students have tremendous capacity for greatness both in their academic pursuits but also in their ability to live, and learn, and love together. I have learnt never to underestimate the capacity of our youth to excel in whatever they do. Sometimes I felt I was more ambitious for our students and staff, than they were for themselves. But I have constantly been surprised by the capacity of young students to rise above bitterness and division, and to make great our campus, country, and continent.

I learnt, again, that the overwhelming majority of our staff and students are good people, respectful of each other, and determined to work together to heal our broken past and build a more just society. And I learnt that it is much more fulfilling to build up than to break down, to embrace than to exclude, and to love than to hate.

Were you frustrated with the pace of transformation?
Sometimes, yes. But fortunately I studied educational organisations all my life, mainly schools and universities. Universities are called institutions for a reason, and on century-old sites like the historic Bloemfontein Campus of the University of the Free State, there are core beliefs, values, and practices deeply ingrained in the culture of the place.

Anyone, therefore, who believes that transformation is easy, has obviously never tried to change an old university. It is difficult. You will get blowback. You will get bad press. You will, sadly, lose the support of some people. Some believe the university is changing too fast while others will tell you it is not changing fast enough. As you press for change, you find the university going two steps forward and one step back; in these circumstances, the solemn duty of the leader is simply to ensure that the overall momentum is always forward.

For such a time as this –
a commemorative journey:
2009-2016 (PDF book)

Description: Prof Jansen commemorative journey2 Tags: Prof Jansen commemorative journey

I therefore budget for disappointment even as I relish the many changes we have experienced together over the past seven years. If you want to obtain an objective sense of the scale of the changes at the UFS, ask those students and staff who were here in 2009, not those who came recently. They will tell you that we have a very different university, even though we all acknowledge that there is still some distance to travel. Our remarkable story of change is told in the recent Transformation Audit of the UFS, chaired by Prof Barney Pityana; that Audit Report will be released after it is read and studied by the University Council at its November meeting.

At an individual level, I learnt that most campus citizens change quickly and others more slowly, and that one has a duty to constantly push for change, but also to be patient about change. And I learnt that the ideal change retains the best of our past even as we embrace a more just and inclusive future in which all campus citizens feel that the university truly belongs to each and every one of them.

Are you optimistic about the future of our university?

Yes. The UFS is a very well-managed university thanks to the exceptional talent in the management of our finances, human resources and information technology environments. By the end of 2016, we will have record enrolments, from undergraduates to doctoral students, which is good for our future income. We run a tight ship with regard to the university’s finances, and we have greatly improved the academic standard of our qualifications; in this regard, I am very proud of my senior management team, and the talented middle management personnel, and those who make things work at the coalface of our operations.

I am very concerned, however, about future funding of the 26 public universities and the extremely vulnerable situation of at least 10 higher-education institutions. The economy is not growing and the costs of running a modern university are escalating. The delays in government commission reports on tuition fees do not help, and there seems no urgency ‘higher up’ to make the tough decisions.

We have to ensure free education for the poorest students — that is the position of your senior management – but we also need to guarantee the financial sustainability of our universities. The task of the UFS leadership, in this period of uncertainty, is to manage those two expectations as best we can. But this cannot happen without your assistance, and I do ask that you provide the new Rector and his or her team with the same understanding and support which I have enjoyed from you.

In conclusion
I am grateful.

To the many hundreds of students who have passed through my office and our home, and who sat in my many lectures and engaged me in your residences – thank you for enriching my sense of life and leadership. I am grateful that Grace and I could support and mentor many of you over the years and see you graduate. I am a better leader because of you.

To the staff of the three campuses – there is no university Rector, I can assure you, who enjoyed more love and support than what you offered me since the day I arrived here. Students come and go, but you have been my foundation year after year, and I thank you for that.

To parents, friends, and followers off-campus, in South Africa and abroad – thank you for hundreds of letters, emails, phone calls, prayers and ‘packages of support’ (from biltong to books). In the most difficult times, you rallied from everywhere with a word of support, often on social media. Know this: your words kept me calm in the storm.

Thank you, everyone.

Goodbye.

Prof Jonathan Jansen
Vice-Chancellor and Rector
University of the Free State

Description: Prof Jansen saying goodbey Tags: Prof Jansen saying goodbey

Prof Jonathan Jansen steps down as UFS Vice-Chancellor and Rector (16 May 2016)

 

 


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