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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

Gender bias still rife in African Universities
2007-08-03

 

 At the lecture were, from the left: Prof. Magda Fourie (Vice-Rector: Academic Planning), Prof. Amina Mama (Chair: Gender Studies, University of Cape Town), Prof. Engela Pretorius (Vice-Dean: Humanties) and Prof. Letticia Moja (Dean: Faculty of Health Sciences).
Photo: Stephen Collett

Gender bias still rife in African Universities

Women constitute about 30% of student enrolment in African universities, and only about 6% of African professors are women. This is according to the chairperson of Gender Studies at the University of Cape Town, Prof Amina Mama.

Prof Mama was delivering a lecture on the topic “Rethinking African Universities” as part of Women’s Day celebrations at the University of the Free State (UFS) today.

She says the gender profile suggests that the majority of the women who work in African universities are not academics and researchers, but rather the providers of secretarial, cleaning, catering, student welfare and other administrative and support services.

She said that African universities continue to display profound gender bias in their students and staffing profiles and, more significantly, are deeply inequitable in their institutional and intellectual cultures. She said women find it difficult to succeed at universities as they are imbued with patriarchal values and assumptions that affect all aspects of life and learning.

She said that even though African universities have never excluded women, enrolling them presents only the first hurdle in a much longer process.

“The research evidence suggests that once women have found their way into the universities, then gender differentiations continue to arise and to affect the experience and performance of women students in numerous ways. Even within single institutions disparities manifest across the levels of the hierarchy, within and across faculties and disciplines, within and between academic and administrative roles, across generations, and vary with class and social background, marital status, parental status, and probably many more factors besides these”, she said.

She lamented the fact that there is no field of study free of gender inequalities, particularly at postgraduate levels and in the higher ranks of academics. “Although more women study the arts, social sciences and humanities, few make it to professor and their research and creative output remains less”, she said.

Prof Mama said gender gaps as far as employment of women within African universities is concerned are generally wider than in student enrolment. She said although many women are employed in junior administrative and support capacities, there continues to be gross under-representation of women among senior administrative and academic staff. She said this disparity becomes more pronounced as one moves up the ranks.

“South African universities are ahead, but they are not as radically different as their policy rhetoric might suggest. A decade and a half after the end of apartheid only three of the 23 vice-chancellors in the country are women, and women fill fewer than 30% of the senior positions (Deans, Executive Directors and Deputy Vice-Chancellors)”, she said.

She made an observation that highly qualified women accept administrative positions as opposed to academic work, thus ensuring that men continue to dominate the ranks of those defined as ‘great thinkers’ or ‘accomplished researchers’.

“Perhaps women simply make realistic career choices, opting out of academic competition with male colleagues who they can easily perceive to be systematically advantaged, not only within the institution, but also on the personal and domestic fronts, which still see most African women holding the baby, literally and figuratively”, she said

She also touched on sexual harassment and abuse which she said appears to be a commonplace on African campuses. “In contexts where sexual transactions are a pervasive feature of academic life, women who do succeed are unlikely to be perceived as having done so on the basis of merit or hard work, and may be treated with derision and disbelief”, she said.

She, however, said in spite of broader patterns of gender and class inequality in universities, public higher education remains a main route to career advancement and mobility for women in Africa.

“Women’s constrained access has therefore posed a constraint to their pursuit of more equitable and just modes of political, economic and social development, not to mention freedom from direct oppression”, she said.

Prof Mama concluded by saying, “There is a widely held agreement that there is a need to rethink our universities and to ensure that they are transformed into institutions more compatible with the democratic and social justice agendas that are now leading Africa beyond the legacies of dictatorship, conflict and economic crisis, beyond the deep social divisions and inequalities that have characterised our history”.

She said rethinking universities means asking deeper questions about gender relations within them, and taking concerted and effective action to transform these privileged bastions of higher learning so that they can fulfil their pubic mandate and promise instead of lagging behind our steadily improving laws and policies.

Media Release
Issued by: Mangaliso Radebe
Assistant Director: Media Liaison
Tel: 051 401 2828
Cell: 078 460 3320
E-mail: radebemt.stg@ufs.ac.za  
02 August 2007
 

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