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Purpose: Pelvic health issues after treatment for gynecological cancer are common. Due to challenges in accessing physiotherapy services, exploring virtual pelvic healthcare is essential. This study aims to understand needs, preferences, barriers, and facilitators for a virtual pelvic healthcare program for gynecological cancer survivors., Methods: A multi-center, sequential mixed-methods study was conducted. An anonymous online survey (N=50) gathered quantitative data on pelvic health knowledge, opportunities, and motivation. Focus groups (N=14) explored patient experiences and consensus on pelvic health interventions and virtual delivery. Quantitative data used descriptive statistics, and focus group analyses employed inductive thematic analysis. Findings were mapped to the capability, opportunity, and motivation (COM-B) behavior change model., Results: Participants reported lacking knowledge about pelvic health interventions and capability related to the use of vaginal dilators and continence care. Barriers to opportunity included lack of healthcare provider-initiated pelvic health discussions, limited time in clinic with healthcare providers, finding reliable information, and cost of physical therapy pelvic health services. Virtual delivery was seen favorably and may help to address motivational barriers related to embarrassment and frustration with care., Conclusion: Awareness of pelvic healthcare is lacking among people treated for gynecological cancer. Virtual delivery of pelvic health interventions is perceived as a solution to enhance access while minimizing travel, cost, embarrassment, and exposure risks., Implications for Cancer Survivors: A better understanding of the pelvic health needs of individuals following gynecological cancer treatments enables the development of tailored virtual pelvic health rehabilitation interventions which may improve access to pelvic health survivorship care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Frequent relapse and chemoresistance cause poor outcome in ovarian cancer (OC) and cancer stem cells (CSCs) are important contributors. While most studies focus exclusively on CSCs, the role of the microenvironment in providing optimal conditions to maintain their tumor-initiating potential remains poorly understood. Cancer associated fibroblasts (CAFs) are a major constituent of the OC tumor microenvironment and we show that CAFs and CSCs are enriched following chemotherapy in patient tumors. CAFs significantly increase OC cell resistance to carboplatin. Using heterotypic CAF-OC cocultures and in vivo limiting dilution assay, we confirm that the CAFs act by enriching the CSC population. CAFs increase the symmetric division of CSCs as well as the dedifferentiation of bulk OC cells into CSCs. The effect of CAFs is limited to OC cells in their immediate neighborhood, which can be prevented by inhibiting Wnt. Analysis of single cell RNA-seq data from OC patients reveal Wnt5a as the highest expressed Wnt in CAFs and that certain subpopulations of CAFs express higher levels of Wnt5a. Our findings demonstrate that Wnt5a from CAFs activate a noncanonical Wnt signaling pathway involving the ROR2/PKC/CREB1 axis in the neighboring CSCs. While canonical Wnt signaling is found to be predominant in interactions between cancer cells in patients, non-canonical Wnt pathway is activated by the CAF-OC crosstalk. Treatment with a Wnt5a inhibitor sensitizes tumors to carboplatin in vivo. Together, our results demonstrate a novel mechanism of CSC maintenance by signals from the microenvironmental CAFs, which can be targeted to treat OC chemoresistance and relapse., (© 2024. The Author(s).)