0
0This research article investigates how targeting the C/EBPα/GREM1/p-ERK signaling axis can reverse resistance to doxorubicin in osteosarcoma, a common primary bone cancer. The study identifies GREM1 as a critical regulator that sensitizes tumor cells to chemotherapy by encouraging mitochondrial fission and triggering ROS-induced apoptosis. Researchers discovered that the transcription factor C/EBPα drives GREM1 expression, while the MAPK/ERK pathway acts as a downstream effector that maintains mitochondrial stability in resistant cells. To combat this, the authors utilized a C/EBPα agonist (ICCB280) and an ERK inhibitor (PD98059) to successfully amplify doxorubicin's lethality in both laboratory and animal models. Ultimately, the findings suggest that manipulating mitochondrial dynamics through these specific molecular targets offers a promising therapeutic strategy for patients with drug-resistant osteosarcoma.
References:
Han Y, Li H, Xue C, et al. C/EBP alpha agonist ICCB280 overcomes doxorubicin resistance in osteosarcoma through mitochondrial dynamics-dependent GREM1-MAPK activation[J]. Cell Death & Disease, 2026.
