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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

Official opening ceremony of the UFS Qwaqwa Campus
2006-02-15

Official opening ceremony of the UFS Qwaqwa Campus
11th February 2006 – Multipurpose Hall

Opening Speech:
Prof. Peter A. Mbati
Campus Principal

Successfully rising to the challenges of incorporations and mergers – developing a vibrant and academically stimulating satellite campus of the University of the Free State.

Thank you Mr. Program Director and good morning ladies and gentlemen.

I wish to once again welcome all of you to the official opening ceremony of the University of the Free State QQ campus.  Thank you for taking time to share with us an important date in our campus academic calendar.  I bring you greetings from our Rector and Vice Chancellor Prof. Frederick Fourie.

During such occasions we try and reflect on important matters that have affected us as an institution in the preceding year, commit ourselves to specific objectives for the current year, while planning for the proceeding year.

Today I shall be talking on Successfully rising to the challenges of incorporations and mergers – developing a vibrant and academically stimulating satellite campus of the University of the Free State’.

SRC inauguration
I would like to congratulate the SRC President and the entire SRC leadership for being elected into important positions of student leadership and authority. 

As a university we are proud of the quality of our student leadership on the Qwaqwa campus.  I am confident that you young leaders will rise to the challenges of your office and discharge your duties with diligence and without fear or favour.  That you will rise above your party affiliations and provide effective leadership to the entire student body on campus.
                              
Leadership is complex and requires you to be objective, just and fair in your approach to the many challenges that you will encounter.  You will be judged not by the populist decision that you take when confronted with difficult choices, but rather, on the wisdom that you exercise in reaching consensus in decision making processes.

The era when management and student leadership viewed each other with suspicion and as adversaries is long gone.  Management, academic and administrative staff, parents and students must have common agendas in as far the  quality growth and development of our university is concerned and to strive towards academic excellence.  I leave the challenge to you students, and more so to the inaugurated student leaders to define your agenda in achieving this noble objective.  I trust that you will make the right choices.

Brief history of incorporation
On the recommendations of the National Working Group of Higher Education, the Qwaqwa Campus of the then University of the North was incorporated into the University of the Free State on 1st January 2003.  We suddenly had to move from a campus that was originally semi-autonomous and with its own culture developed over almost 20 years, into a campus that had to operate as a fully integrated campus of the UFS, a 100 year old institution with its distinct culture.

Following incorporation, we not only had to continue with our core business of teaching, learning, research and community service, but we also had to engage in other important aspects such as exploring the most appropriate models of governance for the campus, encouraging dialogue and interactions at all levels between personnel at the different campuses with a view to developing trust between colleagues. And with the added dimensions such as participation in the transformation task team we in effect are at the fore front of developing a new institutional culture at the UFS and a truly South African University.

UFS Strategic objectives
The strategic and transformation priorities of the University of the Free State for 2006 – 2008 as approved by the Executive Management at its retreat in January 2006 are:

  • Quality and Excellence
  • Equity, diversity and redress
  • Financial sustainability
  • Regional co-operation and engagement

Central to this priority is the integration of the Qwaqwa campus as a valuable constituent part of the UFS, and the strategic reconfiguration of the campus in order that the UFS can play a meaningful role in regional engagement and development.

  • National leadership

The five strategic objectives cannot be viewed in isolation and run simultaneously and in concert with each other. 

The Question must therefore be what we on the QQ campus, staff and students, parents and our broader community are willing to do to achieve these strategic objectives. The reconfiguration and strategic planning of this campus, and therefore its success, must be a collaborative effort between colleagues at QQ and on the main campus.  We must all be ready to work together, to plan together, to shoulder responsibilities together and sometimes, to share the pain and disappointments together. 

The second question must therefore be: are we prepared to go that extra mile for our campus to ensure that we claim our rightful stake within the ranks of well respected academic institutions of higher learning in this country?  At this point in its history this campus requires committed men and women from across the cultural spectrum who appreciate the challenges ahead of us and who are ready to give of their best and to constructively engage at all levels to make this dream a reality.  Because this dream is possible and this dream will be realized!

Quality and Excellence (1st strategic objective)

As mentioned by the Rector in his speech at the official opening ceremony of the university on the main campus on Friday 3rd February, the university will in 2006 pay extra attention to Quality and Excellence.  This is informed by the Higher Education Quality Committee’s (HEQC) institutional audit which is scheduled to take place this year.  Our university as well as several other HEI’s will be subjected to this audit.  This will call for a lot of hard work on your part in preparation for a successful audit and in this regard therefore I request for your cooperation.

As a further step in confirming our commitment to quality and excellence, we have simultaneously introduced on the QQ campus and the main campus workshops on performance management systems to a cohort group.  This will be expanded in 2006 to a wider group of managers on the QQ campus to include among others all Program Heads and Subject Heads. PMS is an invaluable tool for fair, effective and efficient management of a very important resource on campus – the human resource.  Benefits of PMS include among others:

  • Instilling and enriching a culture of performance management (quality assurance) as an integral part of the day to day functioning of staff at the campus
  • Improving staff performance through mentoring, development and training

Tri campus project
One of the more important projects that we as a university undertook in 2005 was the Tri Campus Project which was coordinated by the Free State Higher Education Consortium (FSHEC) through Niel Butcher and Associates consultants.

The Tri-Campus project focused on the strategic planning for higher education campuses in the Free State that have been incorporated with UFS and CUT during the reshaping of the South African higher education landscape. The Bloemfontein Vista campus and the Qwaqwa campus of the University of the North were incorporated with the UFS, and the Welkom Vista campus with the CUT.

The planning process involved a range of research and consultation activities during the course of 2005. This included:

  • Conducting situational analyses of the Qwaqwa campus during which staff and students were widely consulted;
  • Consulting with the campus and with a range of stakeholders in the sub-region
  • Review of the Free State Provincial Growth and Development Strategy and Integrated Development Plans (IDPs) of the regions and other research of relevance to the sub-regions, province and country.

An operational framework for the reconfiguration of the campus with a range of possible Program Qualification Mixes has been produced.  In December 2005, the Rector, the Vice Rector Academic Planning Prof. Magda Fourie and I discussed this document with senior members of the DoE in Pretoria, and we will soon be meeting with the National Minister of Education Me Naledi Pandor for her guidance and to seek support in the further refinement of the document and subsequent implementation.

Recapitalization
This year a further R 6 M has been budgeted for recapitalization.  In about two weeks time the third of phase of renovations on campus will commence and attention will be given to the administration building, the humanities and the outstanding work in the lecture hall complex.  There- after the library, sciences and education buildings will follow.  As you will recall a substantial portion of the R 8.4 million in 2005 was used to upgrade the student residences and the lecture hall complex.

I am certain that the renovations and upgrading of our infrastructure and physical facilities including landscaping will create an enabling environment for you to enjoy your work and studies on this campus.

Renovations come with some measure of inconveniences and I therefore wish to request for your patience and support during this period.

Closing remarks
There is a heightened spirit of optimism on what the future holds for this campus.  This is evident when I talk to a large cross section of staff and students of this campus – and I therefore invite all of you to come and be partners with us on this journey of optimism and hope of what the future holds for the UFS – QQ campus.

Thank you and God bless!

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