Browsing by study line "Translational Research"

Ovarian cancer remains a significant health challenge worldwide, with high-grade serous carcinoma (HGSC) representing its most aggressive subtype. Despite advancements in treatment, disease recurrence remains high, with most patients relapsing within a few years, necessitating the investigation of novel and combination therapies. This study presents a robust framework for evaluating the efficacy of immuno-oncology agents in HGSC through the establishment of a high-throughput patient-derived immunocompetent culture (iPDC) drug screening platform. Using an in-house analysis pipeline to harmonize the complex data outputted by our high-throughput model, we found significant reductions in live tumor cell abundance in response to ataxia telangiectasia and Rad3-related inhibitor (ATRi) in targeting tumor cells irrespective of homologous recombination (HR) status. However, certain samples exhibit immune cell toxicity, emphasizing the importance of assessing immune cell-specific responses for comprehensive evaluation of therapy outcomes. The tissue-based investigation further validates these findings, revealing elevated DNA damage and replication stress biomarker, pRPA32-RPA2(Ser8), expression in responders to ATRi combinations, corroborating previous research and suggesting promising therapeutic targets. Moreover, analysis of immune cell abundance and functional states underscores the predominance of myeloid cells in the tumor microenvironment (TME), with limited variation observed in T-cell activation between responders and non-responders to ATRi. Spatial analysis reveals distinct intertumoral immune infiltration patterns, potentially influencing treatment responses. Overall, these results shed light on the intricate interplay between tumor biology and therapeutic response in HGSC, offering insights into tailored treatment strategies and emphasizing the need for personalized approaches in oncology.