temozolomide

This study establishes FLG as a novel therapeutic target in GBM and validates the suppressive efficacy of cp8 on the characteristics of TMZ resistance, highlighting the translational potential as a multitargeted therapy against TMZ-resistant GBM.

P2, N=35, Active, not recruiting, Washington University School of Medicine | Trial completion date: Sep 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Sep 2026

P2, N=38, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation...Temozolomide in combination with siRNA-mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.

These findings suggest that fulvestrant may be a promising chemosensitizing agent for glioblastoma treated with temozolomide.

P2/3, N=2250, Recruiting, Global Coalition for Adaptive Research | N=1280 --> 2250

It provides a comprehensive perspective on the interplay among sphingolipid dysregulation, immune evasion, TMZ resistance, and the critical functional role of TIMP1. Beyond enabling precise patient stratification, this model highlights specific therapeutic vulnerabilities, offering a translational framework for developing combinatorial strategies to target the sphingolipid regulatory network and overcome GBM chemoresistance.

The PARP inhibitor talazoparib (TAL) combined with the alkylating agent temozolomide (TMZ) produces synergistic cytotoxicity selectively in mtp53, but not wild-type p53 (wtp53), breast cancer cells and organoids. These findings reveal a previously unrecognized mechanism by which the mutant p53-PARP axis enables replication stress tolerance and drives cancer metastasis. We show mutation of p53 in TNBC provides an additional biomarker-guided framework to improve PARPi therapeutic outcomes.

BM03 demonstrated strong chemotaxis toward GBM cells in both in vitro and in vivo models, facilitated by CCR2 and CXCR4 co-expression, which was maintained through tetracycline transactivator (tTA)-mediated transcriptional control...Moreover, repeated BM03 administration, particularly when combined with temozolomide (TMZ), resulted in sustained tumor regression and improved survival. To enhance clinical relevance, we evaluated intraventricular administration, which effectively bypasses the blood-brain barrier and targets dispersed GBM lesions. This study establishes BM03 as a potent, safe, and multifunctional stem cell platform with potential to advance targeted GBM therapy through improved migration, multimodal cytotoxicity, and a strategic administration route for enhanced therapeutic efficacy.

The first-line chemotherapeutic agent Temozolomide (TMZ) for metastatic panNETs faces challenges related to resistance, primarily mediated by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT)...To overcome these challenges, we developed the lipid nanoparticles (LNPs) modified with somatostatin receptors (SSTRs) targeting peptide of Octreotide to codeliver the TMZ and MGMT-siRNA (LOTR) to improve the therapeutic efficacy of TMZ via inhibiting MGMT-mediated resistance and also reducing systemic toxicity caused by TMZ. The in vitro and in vivo results demonstrated that the LOTR system significantly sensitized the tumor response to TMZ, lowered drug resistance, and reduced off-target effects, offering a promising approach for the treatment of advanced panNETs.

Curcumin analogs demonstrate enhanced cytotoxicity in GBM cells, including temozolomide-resistant lines, through multi-target modulation of apoptosis, oxidative stress, oncogenic signaling, and glioma stem cell pathways...Therefore, curcumin analogs have demonstrated significant therapeutic potential as multi-targeting agents to address heterogeneity, treatment resistance, and invasiveness of GBM. However, to realize this potential, there is a need to improve their pharmacokinetics and permeability through the BBB.