Research Articles (Medical Oncology)

Permanent URI for this collectionhttp://hdl.handle.net/2263/4941

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A mixed methods protocol for a framework to improve access to radiotherapy services for cancer patients in Gauteng Province, South Africa
Ramashia, Portia N.; Nkosi, Pauline B.; Bassa, Sheynaz; Mbonane, Thokozani P. (BioMed Central, 2025-11-21)
BACKGROUND : Cancer is a burden on public health worldwide, with its prevalence and mortality continually rising. Radiotherapy, a commonly used modality for the management of cancer, can be used alone or adjuvantly with other cancer treatment modalities for radical and palliative care. However, access to radiotherapy cancer care remained a challenge in many low- and middle-income countries, including South Africa, due to a shortage of equipment, trained personnel, and limited financial resources. This resulted in long waiting times and poor treatment outcomes. A comprehensive strategic framework is being developed to address these issues and improve overall access to radiotherapy for cancer patients in the region. This protocol was for a research study that aimed to develop a strategic framework encompassing policy reforms, infrastructure development, capacity building, and technology integration to enhance access to radiotherapy for cancer patients in Gauteng. METHODS : The study employed a concurrent triangulation mixed methods approach to address the four research objectives, namely: Objective 1: To quantify the current effectiveness of radiotherapy treatment delivery; Objective 2: To assess the socio-economic parameters and demographics that govern access to radiotherapy services for cancer patients in Gauteng Province, South Africa; Objective 3: To explore radiotherapy quality indicators and their impact on patient outcomes, and Objective 4: Based on objectives 1 to 3, develop a practical framework that provides a roadmap for enhancing access to radiotherapy services in Gauteng. Quantitative data (Objectives 1 & 3a) was analysed using IBM SPSS software, while qualitative data (Objectives 2 & 3b) was analysed using ATLAS.ti version 23 through thematic content analysis. Ethical considerations were observed throughout the study. DISCUSSION : The research has the potential to improve access to radiotherapy services. The developed framework will be valuable for policymakers, healthcare providers, and stakeholders in planning and implementing interventions addressing the identified barriers. Enhanced access to radiotherapy services will lead to timely treatment and improved outcomes for cancer patients.
HPV-driven transcriptome and splicing rewiring under SRPK1 inhibition in cervical cancer
Basera, Afra; Alaouna, Mohammed; Duvenhage, Janie; Bates, David Owen; Dlamini, Zodwa; Marima, Rahaba (Frontiers Media, 2026-01-02)
BACKGROUND : Serine/arginine protein kinase 1 phosphorylates serine-arginine-rich (SR) proteins to regulate splice-site selection during alternative splicing. While its role in general RNA regulation is established, its contribution to the HPV-dependent transcriptome and splicing stratification in cervical cancer remains unclear. Therefore, we sought to determine how SRPK1 inhibition differentially remodels gene expression and alternative splicing in HPV+ versus HPV- cervical cancer cells. METODS : HPV16+ SiHa and HPV- C33A cervical cancer cells were treated with the SRPK1 inhibitor, SPHINX31. RNA profiling was performed, and differentially expressed genes were defined as |log2FC| ≥ 1.5. AS events were classified by SUPPA as exon skipping (SE), intron retention (RI), mutually exclusive exons (MXE), alternative 3' splice site (A3SS), and alternative 5' splice site (A5SS). Pathway enrichment was assessed using Gene Ontology/KEGG, STRING protein-protein interaction (PPI) networks, and Molecular Complex Detection (MCODE) was used to identify protein hubs. To determine computational prediction of docking, SPHINX31 was docked into SRPK1 (PDB 5MY8) using SP/XP docking and MM-GBSA rescoring. RESULTS : SRPK1 inhibition was associated with distinct responses that were HPV-related. In C33A cells, upregulated genes were enriched for translation, RNA processing, and glycosylation, with KEGG highlighting ribosome and metabolic modules. Ribosomal hubs dominated the PPI/MCODE, suggesting possible translational and metabolic adjustments. In contrast, SiHa cells exhibited transcriptomic changes consistent with reduced expression of genes linked to Hippo, Wnt, PI3K-AKT, ERK1/2 signaling, migration, angiogenesis, and growth factor cytokine networks. Targets of YAP/TAZ (e.g., CCND1, BIRC5, SNAI2, SERPINE1) and their regulators (RASSF1, CSNK1E) were suppressed. At the splicing level, SiHa cells displayed fewer total AS events but with larger effect sizes, particularly in A3SS/A5SS. C33A cells showed abundant SE (59,234 events; small median ΔPSI) and RI (1,770 events, often binary), including complete shifts in HLA-DRB1/PLIN2 (+1.00) and KLF4 (-1.00). Notable A5SS switches included LEF1 (+1.00) and CDK6 (-1.00) in C33A, and DLX1/MRPL14/THAP5 (-1.00) in SiHa. Docking computationally predicted the low-energy poses of SPHINX31 in the SRPK1 ATP pocket. While not definitive, this evidence may potentially support the transcriptomic and splicing findings. CONCLUSION : SRPK1 inhibition may remodel the cervical cancer transcriptome in an HPV-linked manner, with SiHa cells exhibiting changes consistent with suppression of oncogenic signaling, whereas C33A cells adapt through translational and metabolic reprogramming.
Emerging strategies for targeting vasculogenic mimicry in breast cancer treatment
Sekoba, Nare; Demetriou, Demetra Danielle; Chauke-Malinga, Nkhensani; Mabeta, Peaceful Lucy (Springer, 2026-01-20)
Breast cancer represents the most commonly diagnosed malignancy worldwide and is the fourth leading cause of cancer-related mortality. Approximately 2.3 million new cases of breast cancer were diagnosed worldwide in 2022, accounting for 11.6% of all cancer cases, with approximately 670,000 associated deaths. Breast tumors frequently present with abnormal and highly vascularized networks, promoting accelerated growth and contributing to metastatic potential. Increased vascularization often indicates a more aggressive cancer and significantly affects breast cancer treatment. While angiogenesis offers potential therapeutic targets, it also complicates treatment strategies. Anti-angiogenic drugs such as bevacizumab, which target vascular endothelial growth factor-A signaling, have shown potential in limiting tumor growth. However, their success has been limited, as tumors can develop resistance through alternative pathways. Aggressive breast cancer cells, regardless of estrogen-receptor status, can form vessel-like structures through vasculogenic mimicry. This phenomenon also enables them to evade anti-angiogenic treatment and contributes significantly to tumor resistance to various therapeutic interventions. Moreover, vasculogenic mimicry-positive breast cancer patients exhibit high tumor grade, increased invasiveness, metastasis, and poorer survival outcomes as compared to vasculogenic mimicry-negative breast cancer patients. At present, there are no clinically approved therapies that specifically target vasculogenic mimicry in breast cancer. The intricate molecular mechanisms involved in vasculogenic mimicry within breast cancer present considerable challenges to the development of effective therapeutic strategies. Achieving therapeutic breakthroughs that address this phenomenon would represent a major step in the management of breast cancer. This review examines key molecular pathways that regulate vasculogenic mimicry in breast cancer and assesses the potential of targeting vasculogenic mimicry for therapeutic intervention.
Multi-modal biomarker profiling of tumor microenvironment and genomic alterations to enhance immunotherapy stratification in melanoma
Bida, Meshack; Miya, Thabiso Victor; Marutha, Tebogo; Hull, Rodney; Alaouna, Mohammed; Dlamini, Zodwa (MDPI, 2025-10-03)
Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic alterations to uncover immune escape mechanisms and refine prognostic tools. A structure-based BRAF druggability analysis was performed to anchor the genomic findings in a therapeutic context. Primary cutaneous melanoma cases (N = 205) were classified as brisk (n = 65), non-brisk (n = 60), or absent TILs (n = 80) according to the American association for cancer research (AACR) guidelines. Inter-observer concordance was measured using intraclass correlation. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were graded using immunohistochemistry. Eleven brisk TIL cases lacking TNF-α expression were analyzed using the (Illumina TruSight Oncology 500, Illumina-San Diego, CA, USA). Dabrafenib docking to the BRAF ATP site was performed with Glide SP/XP and rescored with Prime MM-GBSA. Brisk TILs lacking cytokine signals suggested post-translational silencing of TNF-α/IFN-γ. Among the 11 profiled cases, eight exhibited high TMB and copy number alterations, with enrichment of nine metastasis/immune regulation genes. Inter-observer concordance was high (absent TILs, 95%; brisk TILs, 90.7%). BRAF docking yielded a canonical type-I pose and strong ATP pocket engagement (ΔG_bind −84.93 kcal·mol−1). Single biomarkers are insufficient for diagnosis. A multiparametric framework combining histology, cytokine immunohistochemistry (IHC), and genomic profiling enhances stratification and reveals immune escape pathways, with BRAF modeling providing a mechanistic anchor for the targeted therapy.
Computational modelling of Tunicamycin C interaction with potential protein targets : perspectives from inverse docking with molecular dynamic simulation
Naidoo , Vivash; Achilonu, Ikechukwu; Mirza, Sheefa; Hull, Rodney; Kandhavelu, Jeyalakshmi; Soobben, Marushka; Penny, Clement (MDPI, 2025-05-08)
Protein glycosylation plays a crucial role in cancer biology, influencing essential cellular processes such as cell signalling, immune recognition, and tumour metastasis. Therefore, this study highlights the therapeutic potential of targeting glycosylation in cancer treatment, as modulating these modifications could disrupt the fundamental mechanisms driving cancer progression and improve therapeutic outcomes. Recently, Tunicamycin C, a well-known glycosylation inhibitor, has shown promise in breast cancer treatment but remains unexplored in colorectal cancer (CRC). Thus, in this study, we aimed to understand the potential action of Tunicamycin C in CRC using in silico studies to identify possible drug targets for Tunicamycin C. First, we identified two target proteins using the HTDocking algorithm followed by GO and KEGG pathway searches: thymidine kinase 1 (TK1) and cAMP-dependent protein kinase catalytic subunit alpha (PKAc). Following this, molecular dynamics modelling revealed that Tunicamycin C binding induced a conformational perturbation in the 3D structures of TK1 and PKAc, inhibiting their activities. This interaction led to a stable design, promoting optimal binding of Tunicamycin C in the hydrophobic pockets of TK1 and PKAc. Serial validation studies highlighted the role of active site residues in binding stabilisation. Tunicamycin C exhibited high binding affinity with TK1 and PKAc. This study provides a way to explore and repurpose novel inhibitors of TK1 and PKAc and identify new therapeutic targets, which may block glycosylation in cancer treatment.
Targeting SRPK1 to regulate alternative splicing in prostate cancer : the roles of MALAT1 and TUG1
Gabada, Linomtha; Basera, Afra; Alabi, Babatunde Adebola; Dlamini, Zodwa; Mojakgomo, Rahaba Makgotso (Springer, 2026)
BACKGROUND : Prostate cancer (PCa) is a leading cause of cancer-related mortality, with significant racial disparities in outcomes. Long non-coding RNAs (lncRNAs) MALAT1 and TUG1 are implicated in oncogenic pathways. Aberrant RNA splicing, a hallmark of cancer, is often driven by dysregulation of serine-arginine protein kinase 1 (SRPK1), a key spliceosome regulator. The relationship between lncRNAs of splicing factors in cancer pathways remains underexplored, and thus, this study aimed to elucidate the roles of MALAT1 and TUG1 lncRNAs in relation to the SRPK1 inhibitor SPHINX31 in PCa. METHODS : Bioinformatics tools were used to analyze interactions between` MALAT1, TUG1, relevant miRNAs, and target genes. A resazurin assay assessed PCa cell viability (PC-3 vs. HEK293) in response to SPHINX31 at 24 and 48 h. RT-qPCR was used to quantify MALAT1 and TUG1 lncRNAs expression levels. RESULTS : The Alamar Blue assay indicated a time-dependent reduction in PC3 cell viability with 3 µM SPHINX31, particularly at 48 h. RT-qPCR revealed significant regulation of MALAT1 and TUG1, highlighting SRPK1’s role in RNA pathways critical for tumor survival. SPHINX31 induced similar cytotoxic effects in HEK293 cells, illustrating the need for selective tumor specificity. MALAT1 expression was upregulated at 24 h, followed by a decline at 48 h, indicating cumulative cellular stress in PC-3 cells. DISCUSSION : This study demonstrated that SRPK1 inhibition alters lncRNA expression and splicing-related events in PCa. These findings highlight SPHINX31’s potential as a therapeutic agent, especially in combination with treatments like Olaparib, necessitating further optimization for selectivity and reduced off-target effects.
Traditional medicine, environmental exposures, and cultural practices in cancer risk : insights from low- and middle-income countries
Miya, Thabiso Victor; Marima, Rahaba; Marutha, Tebogo; Luvhengo, Thifhelimbilu Emmanuel; Mkhize-Kwitshana, Zilungile; Chauke-Malinga, Nkhensani; Mazibuko, Gugulethu;; Dlamini, Zodwa (Frontiers Media, 2025-10-01)
Cancer is a growing public health concern in low- and middle-income countries (LMICs), influenced by cultural practices, environmental exposures, and dependence on traditional medicine in addition to biological risk factors. Evidence from peer-reviewed publications published between 2010 and 2025 was combined in this narrative review. According to studies, traditional and complementary medicine (T&CM) is used by 35% to 79% of cancer patients in LMICs, which frequently delays biomedical treatment and complicates care. Over 2.4 billion people use biomass fuels for household air pollution (HAP), which has been associated with a two- to three-fold increased risk of lung cancer, especially in women. Furthermore, tobacco smoking contributes to about 2.7 million new cases of cancer in less developed areas each year, highlighting ongoing exposure to avoidable dangers. Findings show that the cancer burden in LMICs is further exacerbated by poor food storage, alcohol use, pesticide exposure, unregulated consumer chemicals, and stigma. These cultural and environmental factors must be addressed in preventative initiatives in addition to biological therapy. Strengthening T&CM regulations, enhancing food safety, upholding alcohol and tobacco legislation, lowering exposures at work and in the home, and introducing culturally-based education to dispel stigma and myths are among the top priorities. This is a narrative review rather than a systematic one; the goal is to map thematic evidence throughout Africa, Asia, and Latin America, providing insights for policy design. Integrated, context-specific, and community-driven approaches are required to eliminate inequities and promote equitable cancer control in LMICs.
Human papillomavirus, human immunodeficiency virus, and esophageal squamous cell carcinoma in South Africa : a study of prevalence, co-infection, and risk factors
Mbatha, Sikhumbuzo Z.; Maphosho, Tania; Ramali, Dakalo; Damane, Botle Precious; Nevhungoni, Portia; Mc-Cabe, Michelle; Mosoane, Benny; Hull, Rodney; Dlamini, Zodwa (Frontiers Media, 2025-08-18)
BACKGROUND : Esophageal squamous cell carcinoma (ESCC) is a serious public health concern in South Africa, ranking among the most lethal malignancies. It has known risk factors including human papillomavirus (HPV). HPV is strongly linked to squamous cell cancers (i.e., cervix, anus, and oropharynx) with human immunodeficiency virus (HIV) shown to increase susceptibility to HPV-related malignancies. The extent to which co-infection with these two viruses contribute to ESCC in South African populations is unclear. This study aimed to determine the prevalence of HPV and HIV in ESCC patients. METHODS : A total of 78 ESCC patients were prospectively recruited between January 2022 and December 2024 at Steve Biko Academic Hospital, Pretoria, South Africa. Participants were assessed for HIV, and tumors biopsied by endoscopy. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens and HPV detection and genotyping were performed. Statistical analyses were conducted using Stata 18, with chi-square tests and logistic regression applied to assess associations, using a significance threshold of p ≤ 0.05. RESULTS AND DISCUSSION : The study population was predominantly Black Africans (96%), 55% male and 45% female, and aged 34–86 years. HIV infection was present in 42.3% (n=33) of patients. High-risk HPV DNA was detected in 56.4% (n=44) of ESCC cases, with high-risk subtypes HPV16 and HPV18 being the most prevalent, found in 68% and 41% of HPV-positive cases, respectively. Co-infection with both HIV and HPV was observed in 23.1% (n=18) of patients. However, statistical analyses showed no significant association between HIV and HPV status in ESCC patients (p = 0.78). However, a trend towards correlation was noted between HIV status and HPV18 positivity (adjusted p = 0.051). CONCLUSION : While no direct association between HIV and HPV in ESCC was found, the high prevalence of high-risk HPV, particularly HPV16 and HPV18, highlights the need for further research. Given South Africa’s burden of HIV and HPV, larger multicenter studies are essential to better understand viral contributions to esophageal carcinogenesis.
Intestinal ischemia–reperfusion and blood–brain barrier compromise : pathways to cognitive dysfunction
Hammed, Opeyemi; Afolabi, Oladele; Ajike, Richard; Hezekiah, Oluwaseun; Alabi, Babatunde Adebola; Ajao, David; Saka, Waidi; Oyekunle, Olubunmi; Olusola, Bamidele (Frontiers Media, 2025-07-15)
Intestinal ischemia–reperfusion (I/R) injury, a disorder occurring from interruption of blood flow to the intestines followed by its restoration, causes a cascade of events leading to systemic consequences, including cognitive impairment. This study analyses the complicated link between intestinal I/R damage and blood–brain barrier (BBB) compromise, highlighting essential processes such as systemic inflammation, gut microbiota dysbiosis, oxidative stress, vagus nerve activation, and altered gut microbial metabolite production. During I/R injury, the weakened gut barrier permits the translocation of microbial products and inflammatory mediators into the circulation, beginning systemic inflammation that disrupts the BBB and exacerbates neuronal damage. Furthermore, gut microbiota dysbiosis and altered gut microbial metabolite synthesis, such as short-chain fatty acids (SCFAs), can impact neuronal signaling and cognitive processes. By delineating these pathways, this study seeks to provide a comprehensive knowledge of the intricate interplay between intestinal I/R injury, BBB integrity, and cognitive function, opening the way for potential therapeutic approaches.
Clinico-pathological and treatment characteristics of HIV and non-HIV related vulvar cancers : analysis of a South African cohort
Sajo, Adekunle Emmanuel; Mnisi, Edwin Francis; Bassa, Sheynaz; Visser, Cathy; Dreyer, Greta (Public Library of Science, 2025-07)
OBJECTIVE : The main objective of this study was to describe the clinical, pathological and treatment characteristics of patients with vulvar cancer who had surgery and or radiotherapy at Steve Biko Academic Hospital. The absolute and relative disease burden, trends over the time period were also analyzed. MATERIALS AND METHODS : This was a retrospective study that described women with vulvar cancer who presented to the Gynaecology Oncology and Radiation Oncology departments of the hospital between January 2012 and December 2022. Their clinical, pathology and radiotherapy treatment records were reviewed for this study. RESULTS : 317 vulvar cancer cases between 2012 and 2022 were included in the analysis. The average age was 45.1±12.7. Forty percent of the participants were younger than 40 years. More than 75% of them were women living with HIV and were all on antiretroviral treatment. The average age of those who were HIV positive was 20 years lower than their HIV negative counterparts, p <0.0001. Their mean haemoglobin (Hb) at presentation was 10.7g/dL. Squamous cell carcinoma was the most common histological type in 96.5% of cases. Sixty four percent of the cases presented in advanced stage. About 48% of those who had primary radiation received curative doses. The median time to completion of radiotherapy treatment was higher among those who received primary radiotherapy as compared to those who received adjuvant treatment, 51.5 vs 46 days, p 0.039. The annual average age decreased from 56 years to as low as 40 years, a mean difference of 16 years, p 0.012. CONCLUSION : It is striking that vulvar cancer is no longer a disease of elderly women. Its incidence is now high among women below 50 years. The study also showed an upward trend in the number of vulvar cancer cases in contrast to the declining average age at diagnosis. There is need for more vulvo-perineal surveillance of HIV positive women to detect early stage of vulvar cancers.
The potential of the South African plant Tulbaghia Violacea Harv for the treatment of triple negative breast cancer
Alaouna, Mohammed; Molefi, Thulo; Khanyile, Richard; Chauke-Malinga, Nkhensani; Chatziioannou, Aristotelis; Luvhengo, Thifhelimbilu Emmanuel; Raletsena, Maropeng; Penny, Clement; Hull, Rodney; Dlamini, Zodwa (Nature Research, 2025-02)
Triple-negative breast cancer (TNBC) is difficult to treat and has a low five-year survival rate. In South Africa, a large percentage of the population still relies on traditional plant-based medicine. To establish the utility of both methanol and water-soluble extracts from the leaves of Tulbaghia violacea, cytotoxicity assays were carried out to establish the IC50 values against a TNBC cell line. Cell cycle and apoptosis assays were carried out using the extracts. To identify the molecular compounds, present in water-soluble leaf extracts, NMR spectroscopy was performed. Compounds of interest were then used in computational docking studies with the anti-apoptotic protein COX-2. The IC50 values for the water- and methanol-soluble extracts were determined to be 400 and 820 µg/mL, respectively. The water-soluble extract induced apoptosis in the TNBC cell line to a greater extent than in the normal cell line. RNAseq indicated that there was an increase in the transcription of pro-apoptotic genes in the TNBC cell line. The crude extract also caused these cells to stall in the S phase. Of the 61 compounds identified in this extract, five demonstrated a high binding affinity for COX-2. Based on these findings, the compounds within the extract show significant potential for further investigation as candidates for the development of cancer therapeutics, particularly for TNBC.
In silico and in vivo toxicity assessment of cysteamine-modified nanoparticles : implications for pharmacotherapy application
Alabi, Babatunde Adebola; Lawal, Sodiq Kolawole; Olojede, Samuel Oluwaseun; Suleiman, Amina; Adesanya, Olamide; Ochuole, Diana Odey; Ogunleye, Fisayo Nathaniel; Ben-Azu, Benneth (Taylor and Francis, 2025)
BACKGROUND : Given the increasing therapeutic potential of cysteamine (CYST) at appropriate doses and expert concerns regarding the toxicity of nanoparticles, this study aimed to assess the toxicity profile of both CYST and silver nanoparticles conjugated with cysteamine (CYST-AgNPs). METHODS : For the acute study, a 300 mg/kg starting dose of CYST (i.p administration) produced a toxic response in some mice (n = 3/group), and a 300 mg/kg beginning dose of CYST-AgNPs produced delayed mild toxicity. Lower doses of CYST and CYST-AgNPs (50, 100, and 200 mg/kg; n = 3/group) were administered (i.p) for further acute toxicological evaluation. The sub-acute toxicity test was conducted for 21 days, and female mice (n = 5/group) were divided into control, CYST (25 and 50 mg/kg), and CYST-AgNPs (25 and 50 mg/kg). AgNPs and CYST-AgNPs were characterized with FTIR spectroscopy, UV spectrophotometer, HR-TEM, and SEM-EDX. Blood samples were collected via cardiac puncture and processed according to the standard hematological analysis protocols. RESULTS : The UV-vis absorbance wavelength range of 400-800 nm was observed. HR-TEM showed mostly spherical nanoparticles ranging from 30 to 90 nm. FTIR showed a functional group of O-H, C = C stretching vibration for AgNPs and O-H, S-H, N-H, C = C stretching vibration for CYST-AgNPs. EDX spectroscopy showed silver, carbon, oxygen, sodium, and chloride elements for AgNPs and CYST-AgNPs. The CYST decreased the WBC, RBC, and platelet counts significantly (p < 0.05), while CYST-AgNPs (25 and 50 mg/kg) reduced only the RBC counts (p < 0.05). CONCLUSION : This investigation presents the in vivo safety analysis and pharmacological potential of cysteamine-modified silver nanoparticles (CYST-AgNPs), suggesting enhanced therapeutic activity.
The histomorphology to molecular transition : exploring the genomic landscape of poorly differentiated epithelial endometrial cancers
Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Mwazha, Absalom; Sebitloane, Motshedisi; Dlamini, Zodwa (MDPI, 2025-03)
The peremptory need to circumvent challenges associated with poorly differentiated epithelial endometrial cancers (PDEECs), also known as Type II endometrial cancers (ECs), has prompted therapeutic interrogation of the prototypically intractable and most prevalent gynecological malignancy. PDEECs account for most endometrial cancer-related mortalities due to their aggressive nature, late-stage detection, and poor response to standard therapies. PDEECs are characterized by heterogeneous histopathological features and distinct molecular profiles, and they pose significant clinical challenges due to their propensity for rapid progression. Regardless of the complexities around PDEECs, they are still being administered inefficiently in the same manner as clinically indolent and readily curable type-I ECs. Currently, there are no targeted therapies for the treatment of PDEECs. The realization of the need for new treatment options has transformed our understanding of PDEECs by enabling more precise classification based on genomic profiling. The transition from a histopathological to a molecular classification has provided critical insights into the underlying genetic and epigenetic alterations in these malignancies. This review explores the genomic landscape of PDEECs, with a focus on identifying key molecular subtypes and associated genetic mutations that are prevalent in aggressive variants. Here, we discuss how molecular classification correlates with clinical outcomes and can refine diagnostic accuracy, predict patient prognosis, and inform therapeutic strategies. Deciphering the molecular underpinnings of PDEECs has led to advances in precision oncology and protracted therapeutic remissions for patients with these untamable malignancies.
From genes to clinical practice : exploring the genomic underpinnings of endometrial cancer
Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Sebitloane, Motshedisi; Dlamini, Zodwa (MDPI, 2025-01)
Endometrial cancer (EC), a prevalent gynecological malignancy, presents significant challenges due to its genetic complexity and heterogeneity. The genomic landscape of EC is underpinned by genetic alterations, such as mutations in PTEN, PIK3CA, and ARID1A, and chromosomal abnormalities. The identification of molecular subtypes—POLE ultramutated, microsatellite instability (MSI), copy number low, and copy number high—illustrates the diverse genetic profiles within EC and underscores the need for subtype-specific therapeutic strategies. The integration of multi-omics technologies such as single-cell genomics and spatial transcriptomics has revolutionized our understanding and approach to studying EC and offers a holistic perspective that enhances the ability to identify novel biomarkers and therapeutic targets. The translation of these multi-omics findings into personalized medicine and precision oncology is increasingly feasible in clinical practice. Targeted therapies such as PI3K/AKT/mTOR inhibitors have demonstrated the potential for improved treatment efficacy tailored to specific genetic alterations. Despite these advancements, challenges persist in terms of variability in patient responses, the integration of genomic data into clinical workflows, and ethical considerations. This review explores the genomic underpinnings of EC, from genes to clinical practice. It highlights the ongoing need for multidisciplinary research and collaboration to address the complexities of EC and improve diagnosis, treatment, and patient outcomes. SIMPLE SUMMARY Endometrial cancer is becoming more common, and current treatments do not work well for everyone. The study aims to understand how genetic changes drive this type of cancer and how these insights can improve treatment. It explores key genetic mutations and how they influence the development of cancer, with the goal of helping to classify the disease more precisely and design targeted therapies that are tailored to individual patients. By connecting genetics to clinical care, this research could lead to earlier diagnoses, better treatment options, and improved survival rates. It also sets the stage for future studies, giving the scientific community a clearer roadmap to enhance cancer care.
Radiogenomic landscape of metastatic endocrine-positive breast cancer resistant to aromatase inhibitors
Khanyile, Richard; Chipiti, Talent; Hull, Rodney; Dlamini, Zodwa (MDPI, 2025-03)
Breast cancer poses a significant global health challenge and includes various subtypes, such as endocrine-positive, HER2-positive, and triple-negative. Endocrine-positive breast cancer, characterized by estrogen and progesterone receptors, is commonly treated with aromatase inhibitors. However, resistance to these inhibitors can hinder patient outcomes due to genetic and epigenetic alterations, mutations in the estrogen receptor 1 gene, and changes in signaling pathways. Radiogenomics combines imaging techniques like MRI and CT scans with genomic profiling methods to identify radiographic biomarkers associated with resistance. This approach enhances our understanding of resistance mechanisms and metastasis patterns, linking them to specific genomic profiles and common metastasis sites like the bone and brain. By integrating radiogenomic data, personalized treatment strategies can be developed, improving predictive and prognostic capabilities. Advancements in imaging and genomic technologies offer promising avenues for enhancing radiogenomic research. A thorough understanding of resistance mechanisms is crucial for developing effective treatment strategies, making radiogenomics a valuable integrative approach in personalized medicine that aims to improve clinical outcomes for patients with metastatic endocrine-positive breast cancer. SIMPLE SUMMARY Breast cancer is a serious health issue worldwide. The endocrine-positive type, which grows in response to estrogen and progesterone, is the most common. Treatments often include aromatase inhibitors. However, some patients become resistant to treatment through genetic changes or changes in cellular pathways. Radiogenomics is a new method that combines imaging processes like MRIs and CT scans with genetic studies. This approach facilitates our understanding of how cancer resists treatment and spreads, especially to the bones or brain. This method helps create personalized treatment plans by connecting imaging results with genetic profiles. With the current state of technology, radiogenomics is looked at as being able to improve the diagnosis, treatment, and outcomes of patients with hard-to-treat endocrine-positive breast cancers.
The exposome perspective : environmental and infectious agents as drivers of cancer disparities in low- and middle-income countries
Dlamini, Zodwa; Alaouna, Mohammed; Marutha, Tebogo; Mkhize-Kwitshana, Zilungile; Mbodi, Langanani; Chauke-Malinga, Nkhensani; Luvhengo, Thifhelimbil E.; Marima, Rahaba; Hull, Rodney; Skepu, Amanda; Ntwasa, Monde; Duarte, Raquel; Damane, Botle Precious; Mosoane, Benny; Mbatha, Sikhumbuzo Z.; Phakathi, Boitumelo; Khaba, Moshawa; Chokwe, Ramakwana Christinah; Edge, Jenny; Mbita, Zukile; Khanyile, Richard; Molefi, Thulo (MDPI, 2025-08)
Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations.
Treatment patterns and clinical outcomes in patients with Hodgkin lymphoma from Saudi Arabia, Turkiye, and South Africa : subgroup analysis from the international multicenter retrospective B-HOLISTIC study
Brittain, David; Akhtar, Saad; Rodrigues, Sylvia; Patel, Moosa; Moodley, Dhaya; Singh, Jaimendra Prithipal; Dreosti, Lydia M.; Mohamed, Zainab; Al-Mansour, Mubarak; Alzahrani, Mohsen; Rauf, M. Shahzad; Maghfoor, Irfan; Besısık, Sevgi Kalayoglu; Boga, Can; Saydam , Guray; Huang , Zhongwen; Pinchevsky , Yacob; Ferhanoglu, Burhan (Galenos Publishing House, 2024-12)
ENGLISH OBJECTIVE : B-HOLISTIC was a real-world retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. MATERIALS AND METHODS : Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or with relapsed/refractory HL (RRHL) from January 2010 to December 2013 were assessed. The primary endpoint was progression free survival (PFS) in patients with RRHL. RESULTS : Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, and cisplatin in Saudi Arabia (78.3%) and dexamethasone, cytarabine, and cisplatin in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1-10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. CONCLUSION : This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with those of Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. These data may serve as a control group for future studies in these countries and inform clinical decision-making.
Sex differences in adiposity and hemodynamic parameters as cardiovascular risk indicators among South African university staff : a descriptive cross-sectional study
Gogoba, Sibusiso; Olojede, Samuel Oluwaseun; Alabi, Babatunde Adebola; Lawal, Sodiq Kolawole; Akpa, Odey; Jegede, Ayoola Isaac; Azu, Onyemaechi Okpara (BioMed Central, 2025-08)
BACKGROUND : Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with their prevalence continuing to rise each year. Adiposity indexes and hemodynamic parameters have been established as effective predictors of CVDs when analysed separately. However, the impact of sex differences on the distribution and combined use of these predictors remains largely unexplored, particularly in Sub-Saharan Africa. This study aimed to investigate the sex differences in the distribution of adiposity indexes (AI) and hemodynamic parameters (HP), as well as their associated indicators of cardiovascular diseases risks among staff members at Walter Sisulu University (WSU). METHODS : This cross-sectional descriptive quantitative study was conducted on 100 healthy adults (50 males, 50 females) aged 18–65 years. AI were assessed using a stadiometer, body composition monitor, and tape measure, while HP were measured with a stethoscope and sphygmomanometer. RESULTS : The study’s findings revealed that mean values for AI, including height, visceral adiposity index, and waist circumference, were higher in males compared to females, while weight, body mass index, and hip circumference were greater in females. Additionally, the study indicated that mean values for HP, such as systolic blood pressure, diastolic blood pressure, and mean arterial pressure, were elevated in males, whereas pulse pressure was higher in females. Notably, heart rate was consistent across both sexes. CONCLUSION : This study provides useful information about the sex-based patterns of adiposity indices and hemodynamic distribution among selected South African populations.
Therapeutic targeting of protein arginine methyltransferases reduces breast cancer progression by disrupting angiogenic pathways
Maphalala, Kamohelo; Ramali, Dakalo Portia; Maebele, Lorraine Tshegofatso; Mulaudzi, Thanyani Victor; Mabeta, Peaceful Lucy; Dlamini, Zodwa; Damane, Botle Precious (Elsevier, 2025-09)
Protein arginine methylation is an epigenetic modification involved in transcription, splicing and signal transduction and is mediated by protein arginine methyltransferases (PRMTs). PRMTs regulate various tumor angiogenesis pathways, including vascular endothelial growth factor receptor-2 (VEGFR-2) signaling. PRMT1, PRMT4, and PRMT5 activate distinct stages of angiogenesis. For example, inhibiting PRMT5 suppresses VEGF-induced vessel sprouting in experimental models while impairing hypoxia-inducible factor 1-alpha (HIF-1α) stability and VEGFR-2 phosphorylation. PRMT1 and PRMT4 similarly influence VEGF isoform expression, leading to increased angiogenesis. Targeting PRMTs in experimental models results in suppressed angiogenesis and reduced cancer progression. Several small-molecule PRMT inhibitors, including GSK3326595 and EPZ015666, have entered early-phase clinical trials for solid tumors. These agents show promise in inhibiting tumor angiogenesis, although there are toxicity concerns. This review examines the mechanistic basis and therapeutic rationale for targeting PRMTs in breast cancer and discusses combination approaches to overcome resistance. We integrate preclinical and emerging clinical data to highlight the potential antiangiogenic and tumor-suppressive effects of PRMT inhibitors, providing insights for future therapeutic strategies for breast cancer. HIGHLIGHTS • Dysregulated arginine methylation may drive aberrant angiogenic signaling pathways in breast cancer. • Arginine methylation controls endothelial cell functions via cytokines, growth factors, and related mediators. • Inhibiting arginine methylation may help counteract dysregulated angiogenic signaling in breast cancer.
AI-powered advances in type II endometrial cancer : global trends and African contexts
Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Sebitloane, Motshedisi; Dlamini, Zodwa (Frontiers Media, 2025-07)
INTRODUCTION : The advent of artificial intelligence (AI) in oncology has opened new avenues for enhancing the diagnosis, treatment, and prognosis of type II endometrial cancers (ECs), which account for the majority of EC-related deaths globally. With rising incidence and increasing concerns in Africa, type II ECs are often detected in advanced stages, exhibit aggressive progression, and resist conventional therapies. Despite these characteristics, they are still treated similarly to type I ECs, which are less aggressive and more treatment-responsive. Currently, no specific targeted therapies exist for type II ECs, creating an urgent need for innovative treatment options. METHODS : This review examines the integration of AI-powered approaches in the care of type II ECs, focusing on their potential to address rising incidence and disparities in Africa. It explores AI-driven diagnostic tools, tailored therapeutic options, and ongoing innovative projects, including efforts to integrate indigenous knowledge into AI applications. RESULTS : AI-powered therapeutic options tailored to the unique clinical profiles of type II EC patients show promise for developing targeted therapies. Several innovative projects are underway, leveraging AI to meet Africa’s unique healthcare challenges. These applications demonstrate significant potential to reduce healthcare disparities and improve patient outcomes, especially in resource-limited settings. DISCUSSION : This review highlights the transformative potential of AI technologies in improving the diagnosis, treatment and management of type II ECs, particularly in Africa, where healthcare disparities are significant. Through the integration of AI in the type II EC care continuum, challenges in African healthcare can be overcome. Innovative projects, leveraging AI to meet the continent’s challenges, have the potential to improve patient outcomes. AI-driven therapies hold the key to personalized oncologic care, and indigenous African knowledge can be used to develop Afrocentric healthcare solutions. In Future, with continued research and the development of robust frameworks and transparent algorithms, investment and collaboration, the potential of AI in Type II EC will be realized.

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