Madré Meyer

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.