Research Articles (Medical Oncology)

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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.
Exosomal long non-coding RNAs in cancer : interplay, modulation, and therapeutic avenues
(KeAi Communications Co., 2024-09) Marima, Rahaba; Basera, Afra; Miya, Thabiso Victor; Damane, Botle Precious; Kandhavelu, Jeyalakshmi; Mirza, Sheefa; Penny, Clement; Dlamini, Zodwa; rahaba.marima@up.ac.za
In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.
From incidence to intervention : a comprehensive look at breast cancer in South Africa
(Springer, 2024-03) Dlamini, Zodwa; Molefi, Thulo; Khanyile, Richard; Mkhabele, Mahlori; Damane, Botle Precious; Kokoua, Alexandre; Bida, Meshack; Saini, Kamal S.; Chauke-Malinga, Nkhensani; Luvhengo, Thifhelimbilu Emmanuel; Hull, Rodney; zodwa.dlamini@up.ac.za
The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities. These concerning trends underscore the urgency of enhancing breast cancer screening while mitigating treatment delays, although obstacles within the healthcare system impede progress. The intersection of breast cancer and human immunodeficiency virus (HIV) further complicates matters and particularly affects the Black population. Tackling the aforementioned disparities in breast cancer in South Africa mandates a multifaceted strategy. Robust screening efforts, particularly those targeting marginalised communities, are crucial for early detection. Concurrently, expedited treatment initiation is imperative. Addressing HIV-related complexities requires tailored interventions to ensure effective care. These multifaceted disparities require pan African research and cooperation as well as tailored interventions to enhance breast cancer care within the African region.
Tumor-infiltrating lymphocytes in melanoma : from prognostic assessment to therapeutic applications
(Frontiers Media, 2024-12) Bida, Nndweleni Meshack; Miya, Thabiso Victor; Hull, Rodney; Dlamini, Zodwa; zodwa.dlamini@up.ac.za
Malignant melanoma, the most aggressive form of skin cancer, is characterized by unpredictable growth patterns, and its mortality rate has remained alarmingly high over recent decades, despite various treatment approaches. One promising strategy for improving outcomes in melanoma patients lies in the early use of biomarkers to predict prognosis. Biomarkers offer a way to gauge patient outlook early in the disease course, facilitating timely, targeted intervention. In recent years, considerable attention has been given to the immune response’s role in melanoma, given the tumor’s high immunogenicity and potential responsiveness to immunologic treatments. Researchers are focusing on identifying predictive biomarkers by examining both cancer cell biology and immune interactions within the tumor microenvironment (TME). This approach has shed light on tumor-infiltrating lymphocytes (TILs), a type of immune cell found within the tumor. TILs have emerged as a promising area of study for their potential to serve as both a prognostic indicator and therapeutic target in melanoma. The presence of TILs in melanoma tissue can often signal a positive immune response to the cancer, with numerous studies suggesting that TILs may improve patient prognosis. This review delves into the prognostic value of TILs in melanoma, assessing how these immune cells influence patient outcomes. It explores the mechanisms through which TILs interact with melanoma cells and the potential clinical applications of leveraging TILs in treatment strategies. While TILs present a hopeful avenue for prognostication and treatment, there are still challenges. These include understanding the full extent of TIL dynamics within the TME and overcoming limitations in TIL-based therapies. Advancements in TIL characterization methods are also critical to refining TIL-based approaches. By addressing these hurdles, TIL-focused research may pave the way for improved diagnostic and therapeutic options, ultimately offering better outcomes for melanoma patients.
Equitable inclusion of diverse populations in oncology clinical trials : deterrents and drivers
(Elsevier, 2024-05) Vidal, L.; Dlamini, Zodwa; Qian, S.; Rishi, P.; Karmo, M.; Joglekar, N.; Abedin, S.; Previs, R.A.; Orbegoso, C.; Joshi, C.; Azim, H.A.; Karkaria, H.; Harris, M.; Mehrotra, R.; Berraondo, M.; Werutsky, G.; Gupta, S.; Niikura, N.; Chico, I.; Saini, Kamalveer S.
The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups.
Directions to overcome therapy resistance in cancer
(Elsevier, 2024-06) Nussinov, Ruth; Weichhart, Thomas; Dlamini, Zodwa; Gibbons, Don L.; Van Seuningen, Isabelle; Konen, Jessica; Ju, Huai-Qiang; zodwa.dlamini@up.ac.za
Novel modalities for treatment of cancer have emerged because of advances in technology that have enabled expansion of our understanding of how cells transform to become cancerous and the role of the tumor microenvironment (TME). However, resistance to therapy poses a major problem for the successful treatment of cancer. Ongoing collaborative efforts of clinicians and researchers from different parts of the world have also led to an emerging understanding of how cancer cells evolve to resist treatment. Jerry Madukwe, the Editor-in-Chief of Trends in Pharmacological Sciences asked experts in the field to reflect on the global challenges in the cancer field and provide their views on what they see as the most pressing questions and research directions to overcome therapy resistance in cancer.

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