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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

Important message to UFS students on NSFAS and financial aid in general

2013-02-01

31 January 2013

Dear Students

There remains some uncertainty as well as misinformation within the student body concerning NSFAS and financial aid in general. This communication is intended to provide the facts on the state of student funding at the University of the Free State (UFS). I hope you find this information helpful and that it would guide you in your decisions as you wait to hear from, or hopefully receive funding from NSFAS or any other source.

Every year the Department of Higher Education and Training (DHET) determines how much funding is available to fund students at all universities in South Africa; this is determined in part by the student numbers. Universities do not ask for, or determine the DHET allocation and are instructed by government that “NSFAS will ensure that the universities comply with the processes, procedures…for the allocated funds.”
On 14 December 2012 the UFS received notice from the DHET that our total allocation would be R108,331,215.66 and that this amount must be apportioned in the following categories:
General NSFAS Funding R85,174,275.07
Teacher Training R2,291,940.59
Disability Funding R1,265,000.00
Final-Year Programme R19,600,000.00
The UFS received 5 952 applications for NSFAS funding and with the available funding we can only finance up to 3 000 students on the Qwaqwa and Bloemfontein Campuses, provided that those students satisfy the stringent criteria, e.g. the so-called “national means test” determined for all universities in the country. If we funded more students that the available monies allow, the university would be held accountable by the NSFAS Board and the DHET and this would threaten future funding.
Students apply in the previous year and therefore late applications are less likely to receive funding.
Academic merit also counts, therefore students who fail one or more modules are less likely to receive new or ongoing support from NSFAS. The combination of academic standing and financial need are among the important criteria in decision-making on NSFAS funds.
The UFS is one of the few universities with a very efficient record in using every cent made available to support poor students; we are proud of this record. No money is sent back to NSFAS, except small amounts not claimed by students in the disability category. The university is not allowed to shift funds between categories as described in point #2 above.
Allocations are not based on campus, but need.
The UFS sets aside an additional R35,7 million (in 2013) from within its own budget as bursaries so that we can accommodate as many students as possible. We spend every cent of this funding on students.
The UFS also raises millions in bursaries from the private sector to support poor and promising students, though these funds are often linked to the industry granting the money, e.g. Investec for Accounting students and SASOL for Chemistry students. This recruitment of bursaries is a 24/7 commitment of the Marketing Office and the Faculties and Heads of Departments are also active in raising funds from government agencies, parastatals and the private sector for students in their units.
After almost all our 2013 funds were allocated in favour of students, we calculated a shortfall in the NSFAS allocation of approximately R51 million. We are in the process of making an urgent submission to NSFAS to consider this additional allocation, but we cannot guarantee that this plea can or will be met.

Finally, I want all our students to know that the University of the Free State works very hard to raise every cent we can to provide poor students with funding for their studies. Many of my colleagues, including support staff, who do not earn very much, use some of their meagre personal resources to help a student with money for registration or clothing or food. In fact, the No Student Hungry Campaign that raises more than R600,000 by UFS volunteers annually, is another mechanism for trying to assist students who might have money for studies, but not much else.

We do this because we care, and because this is what The Human Project at Kovsies is all about.

I therefore ask for your patience as we continue our labour of raising the funds that enable every deserving student to continue their studies at the University of the Free State.

Should you have any further questions about NSFAS, please leave an email inquiry on choanet@ufs.ac.za or mallettca@ufs.ac.za and we will endeavour to provide you with the information you require.

Sincerely Yours

Jonathan D Jansen
Vice-Chancellor and Rector
University of the Free State

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