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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

Inauguration of Prof Francis Petersen as 14th Vice-Chancellor and Rector of the UFS
2017-05-23

Description: Prof Petersen Inauguration Charl Devenish photo Tags: Prof Petersen Inauguration Charl Devenish photo

Dr Khotso Mokhele, Chancellor of the UFS, robes Prof Francis Petersen as Vice-Chancellor and Rector of the UFS.
Photo: Charl Devenish

“At the UFS, we want to produce graduates for the world, and we need to ensure that we use our knowledge to uplift society”
— Prof Francis Petersen, 14th Vice-Chancellor and Rector of the University of the Free State (UFS)

On Friday 19 May 2017, the University of the Free State (UFS) celebrated the inauguration of its 14th Vice-Chancellor and Rector, Prof Francis Petersen. The formal inauguration was held in the Odeion Theatre on the Bloemfontein Campus. The ceremony was preceded by a week-long welcoming programme on the three UFS campuses.

The guest list included representatives from local and provincial government, vice-chancellors and rectors from across South Africa, and senior members of the university’s executive management.

During the inaugural address, Prof Petersen paid tribute to his predecessors for the role they played in making the university what it is today. This included former rectors and vice-chancellors who attended the ceremony, such as Prof Francois Retief and Prof Frederick Fourie, and Prof Stef Coetzee and Prof Jonathan Jansen who were unable to attend.

Prof Petersen characterised 2015 and 2016 as watershed years for the South African higher-education system. “The Rhodes Must Fall, and subsequent Fees Must Fall student and staff protests challenged us, and re-energised a critical engagement around the purpose of the university in an equal society, both as a site of complicity and as a potential agent for social change,” said Prof Petersen.

He committed himself to developing the UFS into an institution that will have an even greater impact than before.

“This institution I am striving to establish will be one that responds positively to inclusivity, diversity, and transformation, and which can incorporate these values into our curriculum, scholarship, and research in a productive way,” said Prof Petersen.

Prof Petersen emphasised the importance of the three-campus model. “The University of the Free State is ONE university with three campuses: the Bloemfontein Campus, our South Campus, and the Qwaqwa Campus. I am committed to align the activities of the three campuses, and to integrate our activities to a greater extent.

“We must work together to infuse each campus with the values we have identified as essential if we are to make our mark as a united University of the Free State: academic excellence, diversity and inclusivity, and innovation.”

The Chancellor, Dr Khotso Mokhele, had the honour of handing over the gown to Prof Petersen. Prof Lis Lange, Vice-Rector: Academic, explained the relationship between the university and the Basotho people, and how this relationship is honoured through the official procession gowns of the UFS. The Basotho blanket is worn by kings, and the university therefore hopes that the symbolism of the gown would be a source of inspiration to Prof Petersen.

The event was concluded by congratulatory messages from former colleagues and the President of the Student Representative Council on the Bloemfontein Campus, SK Luwaca. The event was elegant and graceful – the inaugural address was thought-provoking and inspiring.

 

Official Inauguration Ceremony:

19 May 2017
Bloemfontein Campus

 Description: Official Inauguration photo small Tags: Official Inauguration photo small


"I challenge you to dream big and do big." - Prof Petersen

 

Photo Caption: Dr Khotso Mokhele, Chancellor of the UFS, robes Prof Francis Petersen as Vice-Chancellor and Rector of the UFS.
Photo: Johan Roux

Short biography of Prof Francis Petersen
Inaugural address: 19 May 2017
Transcription of the ceremony
Photo Gallery
Video

 

Welcoming Ceremonies:

The week of 11-19 May 2017 was one of the highlights in this year’s calendar for staff and students of the University of the Free State (UFS), with various ceremonies taking place to welcome Prof Francis Petersen – who assumed his duties on 1 April 2017 – as the 14th Vice-Chancellor and Rector. The festivities culminated in the official inauguration ceremony at the Bloemfontein Campus on 19 May 2017.
 
The Qwaqwa Campus welcoming ceremony took place on Thursday 11 May 2017, attracting a wide spectrum of community leaders from the area. Prof Petersen was welcomed by representatives from the two trade unions, National Education Health and Allied Workers Union (Nehawu) and UVPERSU, as well as representatives from the Student Representative Council (SRC), the Thabo Mofutsanyana Education District, and the House of Traditional Leaders. Paramount Queen Mopeli of the Bakoena Royal House bestowed a special honour upon Prof Petersen by clothing him in a traditional Basotho blanket and hat. She said, "From our heart of hearts, welcome, Prof Francis ..., and all Godspeed during your tenure."
 
The South Campus in Bloemfontein hosted a welcoming ceremony for the new Vice-Chancellor and Rector on 18 May 2017. The ceremony included a number of vocal performances and messages from various stakeholder groups. The same afternoon, the Institute for Reconciliation and Social Justice (IRSJ) also facilitated a panel discussion, titled Diversity, inclusivity, and social justice and the renewed call for decolonisation, in the Albert Wessels Auditorium (AWO) on the Bloemfontein Campus.

The welcoming ceremonies culminated in an event in the Callie Human Centre on Friday 19 May 2017 at the Bloemfontein Campus, with a number of performances by musicians associated with the UFS, marimbas, drum majorettes from Jim Fouche Secondary School, the Grey College Gumboots, and school choirs from Eunice Secondary School, Brebner Primary School, and Willem Postma Primary School. Representatives from key stakeholders such as Nehawu, UVPERSU, the Campus Ministries Forum, SRC, Alumni, Convocation, and the UFS Council had the opportunity to convey their messages of welcome to Prof Petersen.
 
The formal inauguration ceremony took place in the Odeion Theatre on the Bloemfontein Campus the same day.

 

Qwaqwa Campus ceremony:

11 May 2017
Qwaqwa Campus

 Description: Prof Petersen with the queen 2 Tags: Prof Petersen with the queen 2

 

"Qwaqwa Campus is the perfect laboratory for sustainable sciences.” – Prof Petersen

 

Photo caption: Paramount Queen Mopeli of the Bakoena Royal House with Prof Petersen and his wife, Cheslyn.
Photo: Mamosa Makaya

Photo Gallery
Video

Read the full story
Transcription of the ceremony

 

South Campus ceremony:

18 May 2017
South Campus

 Description: South Campus welcoming Tags: South Campus welcoming

 

"South Campus: you aspire excellence, adding to diversity and you are innovative in what you do." - Prof Petersen

Photo caption: Flag bearers and drummers walking to the Madiba Arena.
Photo: Hannes Pieterse

Photo Gallery

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Transcription of the ceremony

 

 

Bloemfontein Campus panel discussion:

Panel discussion: Diversity, inclusivity and social justice and the renewed call for decolonisation
18 May 2017
Bloemfontein Campus

 Description: Panel discussion 18 May 2017 Tags: Panel discussion 18 May 2017


"The UFS should be a place of belonging for everyone." - Prof Petersen

 

Photo caption: from left: SK Luwaca (SRC President, Bloemfontein Campus), Prof Elelwani Ramugondo (UCT), Prof Francis Petersen (UFS), Prof Melissa Steyn (WITS), Prof Andre Keet (UFS)
Photo: Lelanie de Wet

Photo Gallery

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Transcription of panel discussion



 

Bloemfontein Campus ceremony:

19 May 2017
Bloemfontein Campus

 Description: Bloem welcoming ceremony on 19 May 2017 Tags: Bloem welcoming ceremony on 19 May 2017


"I can just say, Wow! I've experienced a lot during the welcoming functions on all three campuses." - Prof Petersen

 

Photo caption: Prof Francis Petersen, Vice-Chancellor and Rector of the UFS
Photo: Rulanzen Martin

Photo Gallery

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Transcription of the ceremony


 

 

Description: Inauguration and welcoming of Prof Petersen combined gallery Tags: Inauguration and welcoming of Prof Petersen combined gallery

Photo gallery of Inauguration and Welcoming Ceremonies

 

 

 

 

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