P04.74 Preclinical evaluation of combinations targeting the DNA damage response in 2D and 3D models of glioblastoma stem cells

摘要

BackgroundDespite surgical resection followed by DNA-damaging adjuvant therapies, glioblastoma remain incurable. Increasing evidence demonstrates that aberrations within the DNA damage response (DDR) of cancer stem cells contribute to treatment resistance. We have previously shown that the Fanconi Anaemia (FA) pathway, a key DDR process, remains inactive in normal brain but is re-activated in glioblastoma, making it an appealing foundational target for cancer-specific combination therapies. Since intratumoural heterogeneity in glioblastoma and inherent capacity for functional redundancy within DDR networks are established concepts - we aimed to determine whether combined and hypothesis-driven targeting of the FA pathway along with interconnected DDR processes could form a basis for effective multimodal therapies.