temozolomide

P1/2, N=68, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

In conclusion, this study identifies a previously uncharacterized HIF-1α/circSPECC1/IGF2BP2/PGK1 axis that drives metabolic adaptation and TMZ resistance in GBM. Targeting this axis overcomes acquired chemoresistance, positioning circSPECC1 as both a prognostic biomarker and a therapeutic vulnerability in hypoxic GBM niches.

P1, N=30, Recruiting, Mayo Clinic | N=10 --> 30

P3, N=408, Recruiting, Alliance for Clinical Trials in Oncology | Not yet recruiting --> Recruiting | Initiation date: Oct 2025 --> Jul 2026

We also discuss therapeutic strategies targeting these miRNA-metabolism circuits, including nanoparticle delivery, dietary restriction, and combination therapies that re-sensitize tumors to temozolomide and radiation. Understanding and therapeutically exploiting these networks presents a powerful approach to overcoming GBM's metabolic resilience, thereby opening new avenues for precision oncology.

P=N/A, N=50, Recruiting, Ottawa Hospital Research Institute | Trial completion date: May 2031 --> Nov 2031 | Trial primary completion date: Nov 2026 --> May 2027

The patient was treated with temozolomide concurrently with radiotherapy, followed by tumor treating fields with adjuvant temozolomide...Various tyrosine kinase inhibitors, including entrectinib, larotrectinib, repotrectinib, and selitrectinib, along with bevacizumab, were considered to potentially prolong progression-free survival and overall survival and improve quality of life. We expect to highlight the rarity of this case while discussing the effectiveness of second-generation tyrosine kinase inhibitors in high-grade glioblastomas with rare gene fusions. We also hope to identify the appropriate timeline and treatment sequence for post-standard care, given the lack of official guidelines regarding cases this infrequent.

Upstream regulators of the homologous recombination (HR) repair pathway are promising targets for overcoming temozolomide (TMZ) resistance. Both compounds inhibited H3K27Ac and were detectable in orthotopic tumors by LC-MS/MS and significantly extended survival alone and in combination with TMZ. These findings suggest that the RBBP4/p300-axis is a key regulator of HR-mediated repair of TMZ-induced DSBs, and inhibition by either CCS1477 or NEO2734 may be beneficial as monotherapy, but further studies are needed to determine the benefit of combining these agents with TMZ.

Clinically, KPNA3 and p-STAT3 protein levels were positively correlated in high-grade glioma tissues. Collectively, our findings suggest that KPNA3 may play a role in concurrently enhances DNA repair and sustains the GSC population to foster TMZ resistance, identifying it as a candidate for further investigation for overcoming chemoresistance in GBM.

qDMA-HP is comparable to pyrosequencing in prognostic effectiveness but is simpler and more cost-effective, suggesting its potential for broad clinical use.

We present a case of a 68-year-old woman with metastatic functional PanNET (VIPoma) who developed a treatment-associated hypermutated, microsatellite instability-high (MSIhigh) phenotype following capecitabine-temozolomide (CAPTEM) therapy. Treatment with pembrolizumab resulted in a robust clinical, biochemical, and radiographic response. This case highlights dynamic genomic evolution in PanNETs and underscores the importance of serial molecular profiling in guiding therapeutic decisions.

We retrospectively analyzed 20 patients with newly diagnosed primary IDH-wildtype glioblastoma who underwent gross-total resection followed by standard radiotherapy and temozolomide treatment between 2016 and 2022...However, given the limited sample size, the selection of extreme survival groups, and the predominance of chromosomal polysomy detected by FISH, these findings should be interpreted as hypothesis-generating only. Further validation in larger cohorts using high-resolution genomic methods is warranted.