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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

UFS responds to concerns around high costs of higher education
2015-10-15

 

Dear Students

UFS responds to concerns around high costs of higher education

There is an understandable and shared concern among students in the country around the high costs of higher education. As you know, this also is a matter of deep concern on our campuses, which the University of the Free State (UFS) has made a priority in discussions with student leaders - and through new strategies to relieve the burden of costs on poor students and their families. In fact, in the past two weeks, the UFS leadership has again engaged students on the matter of fees in the future.

This is what we have done so far. We have maintained our position as one of the universities with the lowest tuition fees in the country. As you would have seen from recent newspaper reports on the cost of a degree at various institutions over the past five years, the UFS has had consistently low fees. This is not an accident; both the University Council and the executive leadership of the UFS is of one mind that we must offer a high quality education at minimum cost to all our students, despite the rising costs of operating a large multi-campus university with 30 000 students. Our commitment to you is to continue to keep those costs to students as low as possible, without compromising on the quality of education.

In addition, we took a decision earlier this year to become the first university to drop application fees for first-year students. We are proud of that achievement, since so many students fall at this first hurdle as they contemplate post-school education and training. We also waived registration fees for postgraduate students and now Research Master’s and PhD students can study tuition free under certain conditions. We raised more than R60 million from the private sector to enable talented students, who do not receive NSFAS funding, to complete their degree studies at the UFS. We set aside some of the university’s own funds to enable even more students to access finance for their studies. And we now have a special office set aside to counsel and assist students to apply for more than one scholarship to support their studies. The university does not follow a policy of maximizing exclusions. It has endeavoured and succeeded to turn around the majority of its potential deregistration cases. During 2015 we had 2 700 students at the risk of being de-registered, but our serious efforts resulted in only over 200 instances of exclusion we could not mitigate. As is the practice for the past few years, these students’ debt for 2015 has been reversed.

But, we do not only look for funds from outside to support our students. Last year we set up a Staff Fund to which ordinary members of the academic and support staff can contribute from their own, and sometimes very modest, salaries to enable Kovsie students to finish their degrees. We have volunteers who work on the No Student Hungry (NSH) Bursary Programme to raise funds for students who cannot afford a regular meal. We have an open line to rural and township schools to nominate poor students with good results for support by the Rector’s Fund, and some of those students are now in their final year of studies. And many of our staff support individual students in their homes and with their families, without being asked to do so. This is what we call the Human Project and it remains central to the way in which we deal with students.

We will of course continue to make representation to government, the private sector, and individuals to increase funding, especially for first-generation students, and for families where more than one student is at university. We will continue to take to the road to raise funds from companies and foundations to finance our students. We will expand on-campus opportunities for limited working hours for students who wish to earn some money to support their studies. As we have said often before, no student who passes all their courses or modules will be turned away simply because they do not have the funds to study.

The UFS discusses and agrees to fee increases with our students well in advance of the next academic year. None of these decisions are taken without the agreement of the student leadership and thus far these engagements, while tough, have always been done in good faith and with the students’ interests at heart.

It is important for you to know that, with the declining government subsidy, in real terms, and the expanding needs of our students, we will not be able to keep the university running without fees - even though this source of revenue comes mainly through scholarships and bursaries. We need to compensate staff, purchase new library books and renew journal subscriptions (which is very difficult given the low value of the Rand), upgrade computers and software, pay rates and taxes, purchase laboratory equipment, pay the water and electricity bills, expand internet services, upgrade campus security, and hire more academics to keep class sizes reasonably small. It is important for you to know that the university has managed to avoid increasing student fees as a result of much higher municipal rates. Our lecturers are not the highest paid in the country and financially we run a tight ship. We consistently achieve unqualified audits and we are known to be one of the universities that manage its NSFAS contributions with great efficiency. We do this because of our commitment to ensure that our students are able to enjoy a high quality of education on a stable campus where there is a deep respect for all campus citizens.

Despite all these efforts, the most important message we wish to communicate, is that the door remains open for continued discussion with student leaders as we continue to find ways of keeping university education open and accessible to all qualifying students. At the same time, the UFS leadership is involved in discussions with government about how to best manage the escalating cost of higher education for our dents.

Thank you for your support and understanding at this time and be assured, once again, of our commitment to students as a matter of priority to the university leadership.

Best regards

Prof Jonathan Jansen
Vice-Chancellor and Rector

University of the Free State
19 October 2015

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