Carla Eksteen

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.

Advancing personalized medicine in LMICs: Predictive indicators for cervical cancer immunotherapy response

The World Health Organization reports that cervical cancer ranks as the eighth most common cancer worldwide and is the ninth leading cause of cancer-related deaths. It is also the most prevalent cancer among women in 25 countries, primarily in Sub-Saharan Africa. Consequently, cervical cancer continues to pose a significant global health challenge, particularly due to the limited treatment options available for advanced stages of the disease. Evidently, immunotherapy is a promising strategy, but its efficacy is variable among patients. As such, predictive indicators are essential for identifying patients who are most likely to benefit from immunotherapy and for guiding treatment decisions. This review provides an overview of the current landscape of predictive biomarkers in cervical cancer immunotherapy, including immune checkpoint molecules, tumor mutational burden and immune cell infiltration. We further discuss additional factors such as cytokines, tumor infiltrating lymphocytes and previous exposure to platinum-based chemotherapy. As the field continues to evolve, ongoing research efforts are needed to refine predictive biomarkers and optimize patient selection in LMICs for immunotherapy in cervical cancer.

A Review: Genetic Mutations as a Key to Unlocking Drug Resistance in Cervical Cancer

Cervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome.