Speaker
Description
Medulloblastoma (MB) and glioblastoma (GB) are highly aggressive brain tu-
mours that exhibit substantial resistance to radiotherapy, largely due to im-
paired DNA damage repair mechanisms. The cellular response to radiation-
induced DNA double-strand breaks (DSBs) is a critical determinant of radiosen-
sitivity. This study investigated the effects of the MDM2 inhibitor AMG232 in
combination with photon irradiation on DNA damage signalling in MB and
GB cell lines using γH2AX foci analysis. Photon irradiation induced a clear
dose-dependent increase in γH2AX foci across all cell lines, confirming effective
DSB formation. Treatment with AMG232 resulted in prolonged persistence
of γH2AX foci, particularly in MB cell lines, indicating delayed or compro-
mised DNA repair. Residual foci detected at later time points suggest increased
reliance on error-prone repair pathways, notably non-homologous end joining
(NHEJ), especially in G0/G1-arrested cells. In contrast, GB cell lines exhib-
ited sustained γH2AX foci levels irrespective of AMG232 treatment, consistent
with intrinsic radioresistance. These findings demonstrate that AMG232 en-
hances radiosensitivity primarily by extending DNA damage signalling rather
than increasing initial DNA damage, highlighting impaired repair kinetics as a
key mechanism influencing treatment response in aggressive brain tumours.
