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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

African Student Affairs Conference a huge success
2011-05-24

 
Mr Rudi Buys, UFS Dean of Student Affairs, Mr. Folabi Obembe, Managing Director of Worldview International, Ms Birgit Schreiber, Director of the Centre for Student support services at the University of the Western Cape, Dr. Augustinah Duyilemi, Dean of Student Affairs at the Adekunleh Ajasin University in Nigeria, Dr. Christina Lunceford, assistant Director for the Centre for Research on Educational Access and Leadership at California State University in America, and Prof. Cecil Bodibe, student affairs veteran and consultant.
Photo: Earl Coetzee

The African Student Affairs Conference (ASAC), which took place on our Main Campus last week, was a major success, with two days of lectures and discussions and two pleasant social gatherings, where delegates had the opportunity to get to know each other.

The conference, hosted on African soil for the first time, and co-hosted by the University of the Western Cape (UWC), started on Wednesday 18 May 2011 with an informal welcoming session. Delegates got to meet each other and Mr Rudi Buys, UFS Dean of Student Affairs, explained the meaning of South African words like "kuier" and "lekker'.

The official start of events took place on Thursday 19 May 2011, in the Reitz Hall in our Centenary Complex. The conference was attended by delegates from universities across the continent and aimed to place the focus on issues relating to student affairs in an African context.

Delegates shared and exchanged strategies, ideas and resources, and discussed issues related to the work of student affairs professionals. The conference hoped to promote an exchange of best practice and assist attendees in identifying successful programmes.

Among the topics discussed on the first day, were “Constructing Post-Conflict Democracy on campus: a case study of transformation of student governance and political engagement as post-conflict intervention”, by Mr. Buys, and a discussion on ways in which social and online media can be used to ease the challenges of student interaction, development and support, by Ms Birgit Schreiber, Director of the Centre for Student Support Services at UWC.

A panel discussion, led by Mr Buys and several members of our Interim Student Council (ISC), discussed the specific challenges faced at the UFS.  The importance of buy-in from role-players in decisions taken by University management in order to ensure their success, was discussed, using the UFS and our recent changes as an example.

The successful integration of residences on campus inevitably came under the spotlight and the recently resolved Reitz-saga was named as a catalyst in getting students less apathetic and more involved in attempts at creating racial and social harmony.

Dr Christina Lunceford, Assistant-Director of the Centre for Research on Educational Access and Leadership at California State University, presented a paper entitled A National Approach to Building Capacity in Student Affairs in South African Higher Education.

She commented on the fact that there is little or no philosophical framework or explicit theory that informs practice of student services in South Africa.

According to Dr Lunceford, student development should be a key concern for every department or unit within student services and emphasized the need for a centralized student development unit at each university.
She also touched on the need for institutions to implement support from international student affairs professional associations, professional development for student affairs practitioners, the utilization of technology to support professionals in the field, and working with international partners to explore future opportunities, as ways in which student affairs can be used to drive performance and change at universities.

The conference continued in the Scaena theatre on Friday 20 May 2011, with presentations by Dr Augustinah Duyileme, Dean of Student Affairs at Adekunle Ajasin University in Nigeria, and Prof. Bobby Mandew, Executive Director of Student Affairs at the University of Johannesburg (UJ).

Dr Duyileme presented a paper on the challenges faced by Nigerian universities with regard to student conflict and protests, which often turn violent, and how such violence can be curbed through proper planning and management.

Prof. Mandew presented a very well-received presentation on UJ’s successful off-campus housing initiative, which involves home-owners and business owners in the areas surrounding their campuses.

Their approach demonstrated how proper planning can prevent problems associated with over-population in private homes and conflict with neighbours of the university, usually related to an influx of students into residential neighbourhoods.

This problem is faced by many universities, as more and more students flock to universities on the continent and campus residents cannot accommodate them.

The conference came to a close on Friday, with most delegates agreeing that the exchange of knowledge which took place was extremely valuable.

Ms Deborah Lahlan, of Nigeria, said: “This is an important conference for Africa and it should become a regular event.”
 

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