Research Articles (Medical Oncology)

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Traditional medicine, environmental exposures, and cultural practices in cancer risk : insights from low- and middle-income countries
(Frontiers Media, 2025-10-01) Miya, Thabiso Victor; Marima, Rahaba; Marutha, Tebogo; Luvhengo, Thifhelimbilu Emmanuel; Mkhize-Kwitshana, Zilungile; Chauke-Malinga, Nkhensani; Mazibuko, Gugulethu;; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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
(Frontiers Media, 2025-08-18) Mbatha, Sikhumbuzo Z.; Maphosho, Tania; Ramali, Dakalo; Damane, Botle Precious; Nevhungoni, Portia; Mc-Cabe, Michelle; Mosoane, Benny; Hull, Rodney; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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
(Frontiers Media, 2025-07-15) Hammed, Opeyemi; Afolabi, Oladele; Ajike, Richard; Hezekiah, Oluwaseun; Alabi, Babatunde Adebola; Ajao, David; Saka, Waidi; Oyekunle, Olubunmi; Olusola, Bamidele
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
(Public Library of Science, 2025-07) Sajo, Adekunle Emmanuel; Mnisi, Edwin Francis; Bassa, Sheynaz; Visser, Cathy; Dreyer, Greta
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
(Nature Research, 2025-02) Alaouna, Mohammed; Molefi, Thulo; Khanyile, Richard; Chauke-Malinga, Nkhensani; Chatziioannou, Aristotelis; Luvhengo, Thifhelimbilu Emmanuel; Raletsena, Maropeng; Penny, Clement; Hull, Rodney; Dlamini, Zodwa; rodney.hull@up.ac.za
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
(Taylor and Francis, 2025) Alabi, Babatunde Adebola; Lawal, Sodiq Kolawole; Olojede, Samuel Oluwaseun; Suleiman, Amina; Adesanya, Olamide; Ochuole, Diana Odey; Ogunleye, Fisayo Nathaniel; Ben-Azu, Benneth
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
(MDPI, 2025-03) Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Mwazha, Absalom; Sebitloane, Motshedisi; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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
(MDPI, 2025-01) Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Sebitloane, Motshedisi; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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
(MDPI, 2025-03) Khanyile, Richard; Chipiti, Talent; Hull, Rodney; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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
(MDPI, 2025-08) 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; zodwa.dlamini@up.ac.za
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
(Galenos Publishing House, 2024-12) 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
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
(BioMed Central, 2025-08) Gogoba, Sibusiso; Olojede, Samuel Oluwaseun; Alabi, Babatunde Adebola; Lawal, Sodiq Kolawole; Akpa, Odey; Jegede, Ayoola Isaac; Azu, Onyemaechi Okpara
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
(Elsevier, 2025-09) Maphalala, Kamohelo; Ramali, Dakalo Portia; Maebele, Lorraine Tshegofatso; Mulaudzi, Thanyani Victor; Mabeta, Peaceful Lucy; Dlamini, Zodwa; Damane, Botle Precious; botle.damane@up.ac.za
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
(Frontiers Media, 2025-07) Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Sebitloane, Motshedisi; Dlamini, Zodwa
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.
Pkhd1l1 : a deafness gene that listens to tumors
(Longdom Publishing, 2024-03) Makrogkikas, Stylianos; Lolas, Georgios; Dlamini, Zodwa; Charitidis, Costas; Syrigos, Konstantinos N.
The PKHD1L1 (Polycystic Kidney and Hepatic Disease 1-Like 1) protein was initially characterized as an inducible Tlymphocyte receptor but has since proved to have many diverse functions. Pkhd1l1 regulates hearing and hippocampal neuronal excitability and protects against epileptic seizures. Its expression is associated with better survival rates in older Lung Adenocarcinoma (LUAD) patients. PKHD1L1 is a potential Tumor-Infiltrating T and Blymphocyte marker (TIL and TIL-B, respectively). In LUAD, PKHD1L1 gene is co-expressed with chemokines such as CCL4, CCL5, CCL19, and CXCL9, attracting T-CD8+ cells to the Tumor Microenvironment (TME). In LUAD, PKHD1L1 transcription primarily correlates with plasma cells, raising the possibility to be involved in Antibody-Dependent Cellular Cytotoxicity (ADCC), Complement-Dependent Cytotoxicity (CDC), and Antibody Dependent Cellular Phagocytosis (ADCP), suggesting its significance in cancer immunity; therefore, Pkhd1l1 is a promising target for therapeutic interventions.
Patients with cervical cancer with and without HIV infection have unique T-cell activation profiles despite similar survival outcomes after chemoradiation
(American Association for Cancer Research, 2025-04) MacDuffie, Emily C.; Cocka, Luis; Lin, Xiang; Bvochora-Nsingo, Memory; Chiyapo, Sebathu; Balang, Dawn; Maswabi, Bokang; Ngoni, Kebatshabile; Ramogola-Masire, Doreen; Zetola, Nicola M.; Wei, Zhi; Shen, Hao; Bassa, Sheynaz; Grover, Surbhi; Robertson, Erle S.
The global burden of cervical cancer is highest in low- and middle-income countries. Women living with human immunodeficiency virus (HIV) infection are particularly affected by cervical cancer despite availability and adherence to antiretroviral therapy. Immune profile correlates of survival and treatment response have not been widely explored in patients with and without HIV infection. This study recruited women with cervical cancer undergoing definitive chemoradiation (CRT) in Botswana. Clinical characteristics and blood samples were collected. Flow cytometry was performed on samples prior to initiation, at completion, and 3 months after CRT. Logistic regression analysis identified immune markers that differed by HIV status and correlated with overall survival (OS). The study enrolled 131 consecutive women (HIV+ N = 89 and HIV− N = 42). From initiation to 3 months after CRT, a significant decrease in CD4 frequency (72%–60.55%, P < 0.001) and an increase in CD8 frequency (20.9%–31.5%, P < 0.001) were seen in women without HIV, whereas no significant changes in CD4 frequency (52.5%–50.9%) or CD8 frequency (39.9%–41.4%) were observed in those with HIV. Peripheral T cells underwent similar activation across the cohort regardless of HIV status. Improved OS was associated with reduced frequency of IL-2–expressing CD4 T-cell subsets. In women living with HIV, enhanced OS was associated with the presence of proinflammatory CD8 T cells. CRT induces peripheral T-cell activation and distinct cytokine profiles that differ by HIV status. Despite similar OS, HIV infection may differentially affect immune response to CRT in women with well-managed HIV. SIGNIFICANCE : Chemoradiation affects the immune system of patients with cervical cancer with well-controlled HIV infection differently than those without HIV, yet their survival does not differ. This finding is an important step in understanding how management of HIV infection can modify cancer outcomes, particularly in settings with a high burden of HIV.
HIV-helminth co-infections and immune checkpoints : implications for cancer risk in South Africa
(MDPI, 2025-03) Damane, Botle Precious; Mulaudzi, Thanyani Victor; Kader, Sayed Shakeel; Naidoo, Pragalathan; Dlamini, Zodwa; Mkhize-Kwitshana, Zilungile Lynette; zodwa.dlamini@up.ac.za
South Africa has the highest HIV prevalence globally, often co-occurring with helminth infections in impoverished regions. The coexistence of these infections leads to immunological interactions, potentially enhancing oncogenesis by upregulating immune checkpoint molecules (ICs) among other effects. Notably, most ICs are overexpressed in cancer and correlated with its progression. Helminth infections trigger Th2-type immunity, increasing immunosuppressive M2 macrophages, regulatory T cells, and associated IC molecules. PD-L2 is reported to contribute to Th2-type immunity induced by helminth infections. Similarly, TIM-3, elevated during chronic viral infections, induces a similar immunosuppressive profile. CTLA-4 and PD-1 impact T-cell function by interacting with CD28, crucial for T-cell function. CD28 is downregulated in chronic infections and cancer. This study investigated the impact of HIV-helminth co-infection on co-stimulatory and co-inhibitory molecule profiles associated with antitumor immunity. Using 78 serum samples collected from March 2020 to May 2021, participants were categorized into uninfected control (no HIV and helminth infections), HIV-infected, helminth-infected, and HIV-helminth co-infected groups. Multiplex immune regulatory molecule assay analysis was conducted. The data were analyzed using multivariate regression analysis and adjusted for confounders (age, gender, BMI, ART, supplements, and other chronic diseases). The uninfected control group was used as the baseline reference group for analysis. HIV-infected individuals had higher PD-1 (adjusted β = 0.12, p = 0.034) and TIM-3 (adjusted β = 23.15, p = 0.052) levels, with the latter showing a trend toward significance. However, lower CD28 levels (adjusted β = −651.95, p = 0.010) were observed. Helminth-infected individuals had higher TIM-3 levels (adjusted β = 20.98, p = 0.020). The co-infected group had higher PD-1 (unadjusted β = 0.18, p = 0.0046) and PD-L2 (adjusted β = 7.95, p = 0.033) levels. A significant decrease in CD28 profile was observed across all infected groups: HIV-infected (adjusted β = −651.95, p = 0.010), helminth-infected (adjusted β = −674.32, p = 0.001), and co-infected (adjusted β = −671.55, p = 0.044). The results suggest that HIV-helminth co-infections alter immune checkpoint markers, potentially increasing cancer risk by promoting an immunosuppressive microenvironment that hinders anti-cancer immunity. CD28’s downregulation underscores immune inefficiency in chronic diseases. Addressing these co-infections is crucial for improving HIV care and potentially reducing cancer risks through targeted strategies.
From genes to clinical practice : exploring the genomic underpinnings of endometrial cancer
(MDPI, 2025-01) Molefi, Thulo; Mabonga, Lloyd; Hull, Rodney; Sebitloane, Motshedisi; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
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.
Characterization of the genomic landscape in HPV-positive cervical and head and neck squamous cell carcinomas by whole genome next generation sequencing
(International Institute of Anticancer Research, 2025-03) Ren, Jianlan; Ma, Nian; Seckar, Tyler; Bassa, Sheynaz; Zetola, Nicola; Grover, Surbhi; Wei, Zhi; Robertson, Erle
BACKGROUND/AIM : In this study, we provide a comprehensive characterization of HPV-positive primary cervical cancers (CC) and HPV-positive head and neck squamous cell carcinomas (HNSCC) through whole genome next-generation sequencing. Human papillomavirus (HPV) infection, recognized as a definitive human carcinogen, is increasingly acknowledged for its role in development of human cancers. HPV-driven cervical cancers are among the leading causes of cancer-related deaths worldwide, while HPV-driven head and neck cancers exhibit distinct biological and clinical characteristics. Recent data has provided convincing evidence that HPV-related cervical cancer, like HPV head and neck cancer also predict better outcomes, with viral integration patterns further predicting disease related outcomes. MATERIALS AND METHODS : We designed an experimental study that encompasses four pairs of HPV-positive patient samples with controls, utilizing state-of-the-art Next Generation Sequencing (NGS) technology including whole genome sequencing, transcriptome sequencing and virus integration. RESULTS : Multiple mutated genes, including TTN, COL6A3, and FLNA, were identified shared between CC and HNSCC. Additionally, we observed a notable proportion of pathways affected by oncogenic alterations, particularly in the RTK-RAS and NOTCH pathways, in both CC and HNSCC. Furthermore, we discovered a shared down-regulation of the Hedgehog signaling pathway based on transcriptome expression analysis in KEGG. We also identified RUNX2 and TFPI as sites of virus integration, and upstream as well as downstream pathway modulators, and represent potential targets for therapeutic interventions. CONCLUSION : Overall, this study showed a thorough comparison between CC and HNSCC from multiple aspects, including gene variations, oncogenic pathways, KEGG enrichment and virus integration sites. However, further studies, which involve larger patient cohorts should be undertaken to further support these findings.
Long intergenic non-coding RNAs and BRCA1 in breast cancer pathogenesis : neighboring companions or nemeses?
(MDPI, 2025-02) Fadebi, Olalekan Olatunde; Miya, Thabiso Victor; Khanyile, Richard; Dlamini, Zodwa; Marima, Rahaba; rahaba.marima@up.ac.za
Breast cancer is one of the leading causes of mortality among women, primarily due to its complex molecular landscape and heterogeneous nature. The tendency of breast cancer patients to develop metastases poses significant challenges in clinical management. Notably, mutations in the breast cancer gene 1 (BRCA1) significantly elevate breast cancer risk. The current research endeavors employ diverse molecular approaches, including RNA, DNA, and protein studies, to explore avenues for the early diagnosis and treatment of breast cancer. Recent attention has shifted towards long non-coding RNAs (lncRNAs) as promising diagnostic, prognostic, and therapeutic targets in the multifaceted progression of breast cancer. Among these, long intergenic non-coding RNAs (lincRNAs), a specific class of lncRNAs, play critical roles in regulating various aspects of tumorigenesis, including cell proliferation, apoptosis, epigenetic modulation, tumor invasion, and metastasis. Their distinctive expression patterns in cellular and tissue contexts underscore their importance in breast cancer development and progression. Harnessing lincRNAs’ sensitivity and precision as diagnostic, therapeutic, and prognostic markers holds significant promise for the clinical management of breast cancer. However, the potential of lincRNAs remains relatively underexplored, particularly in the context of BRCA1-mutated breast cancer and other clinicopathological parameters such as receptor status and patient survival. Consequently, there is an urgent need for comprehensive investigations into novel diagnostic and prognostic breast cancer biomarkers. This review examines the roles of lincRNAs associated with BRCA1 in the landscape of breast cancer, highlighting the potential avenues for future research and clinical applications.

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