Overcoming Intrinsic and Acquired Temozolomide Resistance in Glioblastoma: Fisetin as a Potential Strategy to Enhance Sensitivity via ZEB1 Modulation

Fisetin alone was effective against GB; importantly, the TMZ+fisetin combination demonstrated greater efficacy than TMZ alone by enhancing sensitivity to TMZ through downregulation of ZEB1 in various resistant models, including patient-derived samples. Since ZEB1 is associated with EMT and drug resistance, fisetin may be a promising anticancer candidate to improve chemotherapeutic efficacy in resistant GB and to shed light on personalized treatments, pending further preclinical research.