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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

In January 1, 2003, the Qwa-Qwa campus of the University of the North (Unin) was incorporated into the University of the Free State (UFS).
2003-02-07


FREDERICK FOURIE

IN January 1, 2003, the Qwa-Qwa campus of the University of the North (Unin) was incorporated into the University of the Free State (UFS).

While this is merely the beginning of a long and complex process, it does represent a major milestone in overcoming the apartheid legacy in education, realising the anti-apartheid goal of a single non-racial university serving the Free State.

The incorporation is also part of the minister's broader restructuring of the higher education landscape in South Africa - a process which aims to reshape the ideologically driven legacy of the past.

In contrast to the past educational and social engineering that took place, the current process of incorporating the Qwa-Qwa campus of Unin into the UFS is informed by three fundamentally progressive policy objectives, clearly outlined in the education white paper 3: (A framework for the transformation of higher education):

To meet the demands of social justice to address the social and structural inequalities that characterise higher education.

To address the challenges of globalisation, in particular the role of knowledge and information processing in driving social and economic development.

To ensure that limited resources are effectively and efficiently utilised, given the competing and equally pressing priorities in other social sectors.

Besides informing the way the UFS is managing the current incorporation, these policy objectives have also informed the transformation of the UFS as an institution over the past five years.

In 2001, former president Nelson Mandela lauded the success of the UFS in managing this transformation, by describing the campus as a model of multiculturalism and multilingualism. This was at his acceptance of an honorary doctorate from the UFS.

Indeed our vision for the Qwa-Qwa campus as a branch of the UFS is exactly the same as it is for the main UFS campus - a model of transformation, academic excellence, community engagement and financial sustainability, building on the histories and strengths of both the Qwa-Qwa campus and the UFS (Bloemfontein campus).

Realising this vision will be a giant leap forward in establishing a unified higher education landscape in the Free State.

In more concrete terms, the UFS is working towards this vision by focusing on the following areas of intervention: access and equity; academic renewal; investment in facilities; and sound financial management.

These interventions are being made not to preserve any vestiges of privilege or superiority, but precisely to increase access for students from poor backgrounds and to promote equity and representivity among all staff.

The current growth phase of the UFS has seen student enrolment almost double over the past five years, in particular black students, who now constitute approximately 55 percent of the student population of nearly 18 000 (including off-campus and online students).

But it has not just been a numbers game. Our approach has been to ensure access with success.

Our admissions policy, coupled with the academic support and "career preparation" programmes we offer, have resulted in significant successes for students who otherwise would not have been allowed to study at a university.

This will be continued at Qwa-Qwa as well.

Our academic offerings too have undergone dramatic change. We have become the first university in the country to offer a degree programme based on the recognition of prior learning (RPL).

This is not just a matter of academic renewal but of access as well, especially for working adults in our country who were previously denied a university education.

As for the sound financial management of the UFS (including the Qwa-Qwa campus), this is being done not for the sake of saving a few rands and cents, but for the greater value to our society that comes from having sustainable institutions.

It is sustainable universities that can make long-term investments to fund employment equity, provide information technology for students, upgrade laboratories, construct new buildings, develop research capacity, and provide a safe environment for students and staff, as is happening now at the UFS.

As a result of such management, a practical benefit for prospective students at the Qwa-Qwa campus of the UFS will be lower academic fees in some cases compared with the Unin fees.

As is the case with all these processes, there are concerns from staff and students at Qwa-Qwa and the broader community of the region that the Qwa-Qwa campus serves.

To get the campus viable and to ensure its continuation in the short term, tough choices had to be made by the minister of education regarding which programmes to offer and fund.

But we have been encouraged by the community's understanding that these concerns can be addresed over time as the campus becomes financially viable.

Meetings between the top mangement of the UFS and community representatives, staff and students at Qwa-Qwa have laid the basis for building a climate of trust in such a complex process.

We should not be captives of the past divisions but build this new unified higher education landscape that can meet our country's developmental needs.

It should be a higher education landscape that is based on broadening access, promoting equity and social justice, developing academic excellence, and the effective and efficient management of scarce resources. This should be our common common objective.

Professor Frederick Fourie the rector and vice-chancellor of the University of the Free State (UFS)

 

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