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Researchers develop breast cancer spheroid models to study drug response and resistance

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

UFS awards honorary doctorates during its centenary week

2004-10-07

The University of the Free State (UFS) will award 12 honorary doctorates on Thursday 14 October 2004 to a diverse group of outstanding South Africans and international experts.

This will be the last in a group of 18 honorary doctorates that the UFS will be awarding in its centenary year.

The awards comprise of a number of well-known language experts and writers, experts in higher education, first-time awards in community service and development studies, as well as music.

“This reflects quality and also diversity, a spectrum of convictions as well as the recognition of persons who played a major role in changing society in the last couple of decades, “ says Prof Frederick Fourie, Rector and Vice-Chancellor of the UFS.

The awards can be grouped in the following categories:

Language and literature:

Mr Karel Schoeman (D Litt (hc)) – well-known Afrikaans author and former student of the UFS. Some of the awards he has received include the Hertzog prize for prose (1970, 1986 and 1995), the CNA prize (1972 and 1994), the Old Mutual prize (1985 and 1991), the SABC prize for best television drama in 1990, the M Net book prize in 1997 and the State President award (former President Nelson Mandela: Order for Excellent Service – silver) in 1999. It is an honor for the UFS to have this gifted and creative person among its former students. This conferment is a fitting recognition of his status as leading South African writer.

Ms Antjie Krog (D Litt (hc)) – well-known South African poet and former student of the UFS. Her popularity as poet is evident in her piercing honesty and unequalled power of expression. Some of the awards she has received include the Eugéne Marais prize in 1973, the Rapport prize in 1987, the Hertzog prize in 1990 and the RAU prize in 2000. Her writing has been translated into seven languages. She has also received numerous honors for her involvement in and journalistic documentation of the Truth and Reconciliation Commission’s (TRC) proceedings. It is therefore an exceptional privilege for her alma mater to honor her with an honorary doctorate.

Prof Jaap Steyn (D Litt (et phil) (hc)) – recently, Prof Steyn again distinguished himself as biographer whose thorough research is apparent in the published biographies of illustrious writers such as NP van Wyk Louw and MER. The numerous awards, among which the Stals prize from the South African Academy of Science and Art for the Van Wyk publication, are a matter of record. He conducted the research for this great prize-winning work as honorary professor at the UFS.

Prof Jakes Gerwel (D Phil (hc)) – Chancellor of the University of Rhodes and Director of Naspers, Old Mutual, Gold Fields and Brimstone. His doctoral thesis was published in The Netherlands under the title Literatuur en apartheid. Konsepsies van “gekleurdes” in die Afrikaanse roman tot 1948 (1983). He received an honorary doctorate from Clark College ( Atlanta), the City University of New York and Missouri in the USA, the University of the Western Cape, the University of Cape Town, the University of Natal, Rhodes University, the University of Stellenbosch and the University of the Witwatersrand. He is also outstanding professor in the Humanities at the University of the Western Cape, honorary professor in the Humanities at the University of Pretoria, and was the chairman of the Human Sciences Research Council (HSRC).

Development Studies:

Dr Frederick van Zyl Slabbert (D Phil (hc)) – for his academic achievements, his endeavors for bringing about a peaceful transition in South Africa and his demonstration of the social investment role of the corporate sector. Dr Van Zyl Slabbert has received honorary degrees from the University of Natal and the Simon Fraser University in Canada. He has published seven books and various academic articles.

Community Service:

Prof Robert G Bringle (D Phil (hc)) – from the Indiana University-Purdue University Indianapolis (IUPUI) in the USA. He is currently Chancellor’s Professor of Psychology and Philanthropic Studies at the IUPUI and also Director of the IUPUI’s Centre for Service Learning. He is honored for his exceptional contribution to several of the UFS’s community service projects as well as his role in the advancement of a multi- and inter-disciplinary approach to academic development and the integration of service learning within the faculties of the UFS. He has also made a valuable contribution to the conceptual framework of the UFS’s unique community service policy and more recently to the advancement of a research culture regarding community service.

Higher education:

Dr Khotso Mokhele (D Phil (hc)), President of the National Research Foundation (NRF) is honored for his contribution to the South African higher education sector. He has also made a substantial contribution to the development of the research capacity of universities and technikons in South Africa. Dr Mokhele was born in Bloemfontein and matriculated at the Moroka High School in Thaba Nchu.

Prof Saleem Badat (D Phil (hc)), the Chief Executive Officer of the Council on Higher Education (CHE). Prof Badat has devoted himself to transforming and building South African higher education, and has constantly challenged the higher education sector to retain the moral basis of higher education and tackle its challenges with intellectual honesty, ingenuity, creativity and courage. He is honored for his intellectual leadership in the development of a equitable, just and quality higher education system in South Africa.

Law:

Prof HA (Boelie) Wessels (D Legum (hc)) – for his contribution to the fields of Roman Law, Legal History at the UFS. He is currently a part-time lecturer at the UFS’s Faculty of Law.

Medicine:

Prof CJC Nel (D Phil (hc) Posthumous) – for the way in which he strived for the advancement of excellent medical education in the country. Prof Nel also did pioneering work in the field of transformation in higher education. Under his guidance the School of Medicine at the UFS became one of the first medical schools to adopt a parallel-medium system of instruction.

Music:

Prof Leo Quayle (D Mus (hc)) – for the significant contributions he has made to the development of music – not only in Bloemfontein, but also on national level and abroad. His initiative, enthusiasm and dedication contributed to the eventual founding of the Free State Musicon, as well as the first symphony orchestra and the first string quartet in Bloemfontein. Prof Quayle is a former head of the Department of Music at the UFS.

Prof Jack de Wet (D Mus (hc)) – well-known for his exceptional contribution to violin tuition in South Africa. As pedagogue of international stature, he still moulds violinists who compete at national and international level. At an advanced stage of his career, he still actively conveys his knowledge, experience and distinctive insight in his field of speciality to yet another new generation of young violin teachers. Today the symphony orchestras in Bloemfontein and Port Elizabeth also stand on the foundations laid by him.

Media release
Issued by: Lacea Loader
Media Representative
Tel: (051) 401-2584
Cell: 083 645 2454
E-mail: loaderl.stg@mail.uovs.ac.za
7 October 2004

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