Conectar
by Jakob Brandstetter, Lea Goldstein, Tim Schreiber, Rupert Palme, Tobias Lindner, Markus Joksch, Bernd Krause, Brigitte Vollmar, Simone Kumstel
Pancreatic cancer is the third leading cause of cancer-related death, with a 5-year survival rate of only 10%. Preclinical studies remain essential for identifying novel therapeutic strategies, discovering biomarkers, and deepening the understanding of disease biology. The most frequent driver mutation in pancreatic cancer is the G12D mutation in the KRAS gene, present in approximately 90% of the tumors. A recent study demonstrated complete regression of KRAS-driven pancreatic cancer upon systemic ablation up- and downstream signaling proteins EGFR and C-RAF. Building on these findings, we investigated the therapeutic benefit of combining the EGFR inhibitor erlotinib with the novel pan-RAF inhibitor LXH-254. The anticancer effects of this combination were assessed in vitro in murine and human pancreatic cancer cell lines by evaluating cell proliferation, cell death and phosphorylation of key signaling proteins. Subsequent in vivo studies were performed in an orthotopic murine pancreatic cancer model and in genetically engineered KPC mice, using daily oral administration of LXH-254 (35 mg/kg) and erlotinib (75 mg/kg). While the treatment robustly inhibited MAPK signaling and caused significant anti-proliferative effects in vitro, it did not improve survival or reduce tumor burden in either in vivo model. hese results contrast with previous reports of efficacy from monotherapies in xenograft models, highlighting the limitations of current preclinical approaches. Our findings underscore the need to develop more effective pathway-targeted inhibitors, and preclinical models that predict clinical outcomes more accurately.Health literacy (HL) is essential for making informed health-related decisions, for example enabling parents to reduce their child’s allergy risk. Health literacy does not, however, rely solely on an individual’s capacities, but is strongly influenced by external factors. Midwives provide important health advice to families, particularly since their relationship is close during a time of significant transition. This offers them a unique opportunity to positively influence the HL of parents, which in turn may support the health and well-being of the whole family. The aim of this study is to develop and evaluate an intervention that can support midwives in providing allergy prevention advice in a way that is in line with the concept of HL.
In accordance with the recommendations of the Medical Research Council framework in the first phase of this study, we will survey midwives (target sample size=379) in Germany regarding their practices, the potential barriers they face and enabling factors in providing advice on early childhood allergy prevention in an HL-responsive way. The data will be subjected to descriptive statistical analysis. Two co-design workshops will then be conducted with various stakeholders in two regions (Rhineland-Palatinate and Saxony) of Germany. Following the protocol proposed by the Stanford Design Thinking School, we will use design thinking to collect ideas for the intervention. Based on these ideas and our previous qualitative and quantitative study, we will develop an intervention in collaboration with didactic experts. The intervention will be piloted in three groups (midwives=10–15, midwives working as practice supervisors=5–10, students of midwifery=10–20). For the process evaluation, we will use observation protocols of the intervention conduct and qualitative interviews. For the outcome evaluation, we will use a questionnaire and observations in simulation laboratories with students of midwifery.
This study protocol was approved by the Ethics Committee of the University of Regensburg (ID 23-3441-101) and is in compliance with the Declaration of Helsinki. Participation in the study will only be possible after informed consent has been given. Our results will be presented at national and international conferences and published in scientific journals. Additionally, once it has been finalised, we will make the intervention available to educational institutions for (future) midwives.
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