Anna‐Mart Engelbrecht

Resveratrol: Sensitising CD44+ Cervical Cancer Cells to Carboplatin and Mitigating Metastasis

ABSTRACT Background Cervical cancer remains a leading cause of cancer‐related mortality among women globally. Persistent infection with high‐risk human papillomavirus drives cervical carcinogenesis, and treatment outcomes are frequently challenged by metastasis and chemoresistance. The transmembrane glycoprotein cluster of differentiation 44 (CD44), a marker associated with cancer stem cells (CSCs), has emerged as a critical mediator of both processes in cervical cancer. Objective This review aims to critically evaluate current evidence on the role of CD44 in cervical cancer progression, metastasis, and treatment resistance. It also explores the potential of resveratrol, a naturally occurring polyphenol with known anticancer properties, as a chemo‐sensitizing agent to carboplatin therapy. Methods A comprehensive review of the literature was conducted using databases such as PubMed, Google Scholar, and Scopus to identify studies that investigate CD44‐mediated mechanisms in cervical cancer, as well as the modulatory and mechanistic effects of resveratrol on CD44 and chemoresistance across various cancer types. Results CD44 has been consistently implicated in promoting drug resistance, epithelial‐to‐mesenchymal transition (EMT), and stemness in cervical cancer. Resveratrol has demonstrated antimetastatic and chemo‐sensitizing effects in several malignancies, such as colorectal and breast cancers, often through modulation of CD44 and associated pathways. However, direct evidence in cervical cancer remains limited. Conclusion Current findings suggest a promising therapeutic avenue for combining resveratrol with carboplatin to overcome CD44‐mediated treatment resistance and metastasis in cervical cancer. Nonetheless, further cervical‐specific studies are needed to validate this approach. A clearer understanding of this relationship may facilitate lower chemotherapy dosing, reduced toxicity, and improved clinical outcomes.

Targeting treatment resistance in cervical cancer: A new avenue for senolytic therapies

Cervical cancer poses a significant global health challenge, particularly impacting women in economically developing nations. This disparity stems from a combination of factors, including inadequate screening infrastructure and resource limitations. However, the foremost contributor is the widespread lack of awareness and limited accessibility to Human Papillomavirus (HPV) vaccination, which is a key preventative measure against cervical cancer development. Despite advancements in cervical cancer prevention, treatment resistance remains a major hurdle in achieving improved patient outcomes. Cellular senescence, specifically the senescence-associated secretory phenotype (SASP) and its bidirectional relationship with the immune system, has been implicated in resistance to conventional cervical cancer chemotherapy treatments. The exact mechanisms by which this state of growth arrest and the associated changes in immune regulation contribute to cervical cancer progression and the associated drug resistance are not entirely understood. This underscores the necessity for innovative strategies to address the prevalence of treatment-resistant cervical cancer, with one promising avenue being the utilisation of senolytics. Senolytics are agents that have promising efficacy in clearing senescent cells from tumour tissues, however neither the utilisation of senolytics for addressing senescence-induced treatment resistance nor the potential integration of immunotherapy as senolytic agents in cervical cancer treatment has been explored to date. This review provides a concise overview of the mechanisms underlying senescence induction and the pivotal role of the immune system in this process. Additionally, it explores various senolytic approaches that hold significant potential for advancing cervical cancer research.

Personalised Medicine in Cervical Cancer: Evaluating Therapy Resistance Through Multi‐Model Approaches

ABSTRACTIntroductionCervical cancer remains a leading cause of malignancy among women globally, disproportionately affecting women from low‐to‐middle‐income countries, including South Africa. The high prevalence in impoverished communities places significant pressure on the public healthcare system. In these regions, human papillomavirus (HPV); the primary risk factor for cervical cancer—along with co‐occurring immunosuppressive conditions such as HIV, is common. Compounding this burden is the widespread development of treatment resistance to conventional therapies like cisplatin and carboplatin. Resistance is frequently associated with therapy‐induced cellular senescence, underscoring the need for more personalised treatment strategies tailored to individual patient profiles.Methods and MaterialsThis study aimed to assess ex vivo methods' utility in predicting patient‐specific therapy responses. Biopsy samples from cervical cancer patients were cultured and subjected to various chemotherapies. Cell viability, senescence markers and treatment resistance pathways were analysed to determine optimal treatment outcomes.ResultsThe findings revealed significant variability in optimal treatment responses, with ex vivo methods demonstrating limitations in fully capturing the complexity of patient‐specific reactions to therapy. No single experimental model provided comprehensive predictive insights into treatment outcomes.ConclusionThis study underscores the need for integrative and multidisciplinary approaches when evaluating treatment strategies for cervical cancer. While ex vivo models offer valuable insights, combining multiple experimental methods is crucial for a more reliable and comprehensive understanding of treatment response and resistance mechanisms. Standardiszing approaches or employing method combinations may enhance personalised medicine efforts, particularly in resource‐limited settings.

Inflammation and thrombotic risk in late-stage cervical cancer: An exploratory study of coagulation and cytokine profiles in a South African cohort

This exploratory study investigates the possible relationship between inflammation and thrombosis in cervical cancer patients in South Africa, highlighting the need for improved thrombotic risk profiling. Thromboelastography (TEG) was used to assess coagulation parameters in platelet-poor plasma (PPP) from a small cohort of late-stage (III and IV) cervical cancer patients (n = 19) and healthy controls (n = 15). Parameters assessed included clotting time, clot formation speed, and clot strength. A Luminex Multiplex assay was used to measure interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, vascular endothelial growth factor-A (VEGF-A), and tumour necrosis factor-α (TNF-α) in PPP. Haematological profiles were also evaluated. Cervical cancer patients displayed a significantly shortened clotting time (p = 0.0044) and increased clot strength (p = 0.0003), suggesting enhanced coagulation. IL-1β was notably elevated (p = 0.0200), consistent with an inflammatory environment. Higher lymphocyte, neutrophil, and platelet counts (p = 0.0162, 0.0420, and 0.0374, respectively) were observed, indicating a possible prothrombotic state. These findings suggest a potential link between inflammation and thrombosis in cervical cancer patients. However, due to this study's small sample size and exploratory nature, direct relationships between these factors have yet to be definitively established and remain speculative. Thrombotic risk profiling may still offer value in managing patients, but further investigation is required to confirm these preliminary observations.