Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11. (PubMed, Front Oncol) - Dec 24, 2024 - "Using erastin and sulfasalazine, both inhibitors of SLC7A11 and activators of ferroptosis, we were able to reverse the antagonistic effects of ERK1/2 inhibitors and demonstrate a strong synergistic action in vitro and in vivo in zebrafish models. These results demonstrated a pivotal role of the RAS-MAPK pathway in the NB cellular response to APR-246 via the modulation of intracellular concentrations of GSH and the transport of cystine through SLC7A11, phosphorylation of Hsp27, and programmed cell death. Combining APR-246 with RAS-MAPK pathway inhibitors can, in some cases, lead to antagonistic action, which can be reversed by combining APR-246 with the clinically approved drug sulfasalazine."
Journal • CNS Tumor • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • BCL2L11 • SLC7A11
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Fabienne Gumy-Pause; Ina Oehme; Laurence Lesne; Marc Ansari; Sara Najafi; Vid Mlakar
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