EPIC-1042 as a potent PTRF/Cavin1-Caveolin-1 interaction inhibitor to induce PARP1 autophagic degradation and suppress temozolomide efflux for Glioblastoma.

Biao HongEryan YangDongyuan SuJiasheng JuXiaoteng CuiQixue WangFei TongJixing ZhaoShixue YangChunchao ChengLei XinMenglin XiaoKaikai YiQi ZhanYaqing DingHanyi XuLongtao CuiChun-Sheng Kang

Published in: Neuro-oncology (2023)

EPIC-1042 reinforced the effect of TMZ by preventing TMZ efflux, inducing PARP1 degradation via autolysosomes to perturb the BER pathway and recruitment of MGMT, and inhibiting autophagy flux in the later stage. Therefore, this study provided a novel therapeutic strategy using the combination of TMZ with EPIC-1042 for glioblastoma treatment.

Keyphrases

cell death
dna damage
dna repair
signaling pathway
oxidative stress
endoplasmic reticulum stress