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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

State of our campuses: UFS closes campuses until Friday 28 October 2016 to readjust academic programme
2016-10-15

UFS announces strategy for completion of the 2016 academic year

Agreement between UFS management and student leadership in relation to residences

After almost four weeks of student protests about fees at the University of the Free State (UFS) and the subsequent suspension of the academic programme and closing of campuses, the senior leadership announced on 14 October 2016 a strategy to ensure that students will be able to complete the 2016 academic year.

The university on 13 October 2016 announced that it will shut down its Bloemfontein and South Campuses until 28 October 2016 for crucial and complex arrangements to be put in place to readjust the academic calendar and ensure that all students can complete their studies. The senior leadership did, however, make it clear that the university will not be shutting down for the remainder of 2016.

No teaching and learning activities at undergraduate and honours level will be offered between 17 October and 28 October 2016. The university will re-start teaching and learning at undergraduate and honours level in the first week of November 2016.

However, teaching and learning will not take place in the classrooms during November 2016, but through a different mode of delivery that consists of a combination of printed and recorded lectures, study materials and learning aids that will be provided by the university and delivered through Blackboard. In this manner no attempts at disrupting the rest of the academic year will affect our students’ academic programme. Students, however, will sit for the exam on campus.

Students in residence accommodation can return to campus as from 29 October 2016 and it is recommended that students who do not have off-campus internet access return to campus in order to access study material to complete the academic year.A new timetable for exams is still being developed and will be communicated as soon as the arrangements have been finalised.

Faculties have been differently affected by the loss of teaching time. Some faculties like the Faculty of Law have completed their curriculum, while other faculties like the Faculty of Natural and Agricultural Sciences require more teaching time. Some faculties, like the Faculty of Health Sciences, cannot do teaching through alternative modes of delivery.

The needs of the different faculties have been taken into account for developing a rescue plan to complete the 2016 academic year.

  • The Faculty of Health Sciences will continue its classes and clinical rotations as normal for all three schools on the Bloemfontein Campus and in the relevant hospitals. All students registered in programmes in the Faculty of Health Sciences will stay in residences for the full period of their studies and exams. Final-year medical students will graduate in December 2016 as expected.
  • In the Faculty of Economic and Management Sciences, final-year students for the Certificate in the Theory of Accounting (CTA) will stay on campus during October through to December 2016 and their classes and tests will not change.
  • Arrangements for all other faculties and programmes are being prepared and within the next week, students and parents/guardians will receive communication about how curriculum content will be completed and when the final exams will take place.
  • The university is extending the academic year so that we can recuperate all the lost teaching and learning time. The qualifications conferred on the 2016 class will be of the same quality and standards as all UFS qualifications.

The UFS is and will remain a fundamentally contact teaching and learning education university. However, under the current circumstances faced not only by the UFS, but higher-education institutions across the country, the best way of ensuring the integrity of the academic programmes in most faculties is by using an alternative way of teaching and learning. Other South African universities have chosen the same approach to be able to complete the academic year.

Instead of students going to class, they will have content delivered to them where they are (library, computer labs, their own computers, etc.) through Blackboard and printed and electronic material. This is a different way of learning but students will be carefully guided and supported.

Faculties are currently preparing all the necessary materials and instructions to support student learning.Standards and quality will be the same as if students were attending classes. Some faculties require practical laboratory work as part of their curriculum. The exam timetable will be adapted for these students to be able to complete their practical work when the academic activities commences in November 2016. The relevant faculties will communicate the schedule of practical work directly to the students.

Students in their final year will complete their studies during 2016. It is possible that in some cases the graduation ceremony for these students will be in June 2017 instead of April 2017. This will not prejudice students with bursaries, or committed employment in law firms or other businesses. The university will provide the necessary academic transcripts as proof of the completion of the relevant qualifications. None of these changes will affect postgraduate students.

The university will maintain regular communication with students and parents/guardians to update them on the new exams timetable.Faculties will communicate directly with students about issues related to their programmes.

“One of the areas in which significant progress was made, is that we were able to agree on a basis for stability with student leaders. The student protests occurred during an important time in the university’s academic calendar and the readjustment of our academic programme has put tremendous pressure on academic and support services staff, and created anxieties for parents,” said Prof Nicky Morgan, Acting Rector of the UFS.

“The senior leadership restates its commitment to free education as well as its willingness to stand together with students and other public universities to impress on government the urgency to decide on a time frame for the roll-out of free higher education for the poor and missing middle. We will use the next two weeks to meet with the leadership of Universities South Africa to coordinate collective action in this regard. We will furthermore also roll out a series of activities to inform and educate students and the general public on different models and experiences of providing free higher education,” he said.

The strategy to readjust the 2016 academic year is applicable to students on the Bloemfontein and South Campuses.


Released by:
Lacea Loader (Director: Communication and Brand Management)
Telephone: +27 51 401 2584 | +27 83 645 2454
Email: news@ufs.ac.za | loaderl@ufs.ac.za
Fax: +27 51 444 6393

 

State of our campuses #15: UFS closes campuses until Friday 28 October 2016 to readjust academic programme

State of our campuses #14: All academic activities on UFS campuses remain suspended on 13 and 14 October 2016

State of our campuses #13: Availability of information about plans for remainder of UFS 2016 calendar year

State of our campuses #12: All academic activities at UFS campuses suspended for 11 and 12 October 2016

State of our campuses #11: Academic activities on UFS campuses continue

State of our campuses #10: Impact of non-completion of the 2016 academic year on UFS students 

State of our campuses #9: Academic programme on all UFS campuses to resume on Monday 10 October 2016

State of our campuses #8:  UFS extends vacation as from 28 September until 7 October 2016, 28 September 2016

State of our campuses #7: All three UFS campuses will be closed today, 27 September 2016.

State of our campuses #6: All UFS campuses reopen on Tuesday 27 September 2016

State of our campuses #5: UFS campuses to remain closed on Monday 26 September 2016

State of our campuses #4: Decisions about the UFS academic calendar

State of our campuses #3: UFS campuses closed until Friday 23 September 2016 

State of our campuses #2: UFS Bloemfontein and South Campuses closed on Tuesday 20 September 2016 (19 September 2016)

State of our campuses #1: Academic activities suspended on UFS Bloemfontein Campus (19 September 2016)

 

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