temozolomide

TMEM5 is associated with circadian-gene expression patterns, temozolomide response, and bioenergetic readouts in GBM models. TMEM5 knockdown was accompanied by altered time-dependent expression profiles of multiple clock genes, reduced OCR/ECAR parameters under the tested conditions, and increased TMZ sensitivity. These findings support TMEM5 as a circadian-associated factor in GBM and provide a rationale for future studies to define whether TMEM5 directly influences circadian regulation and metabolic pathway remodeling in vivo.

Our findings reaffirm the dismal outcomes of pediatric H3 G34-mutant DHG, which exhibits radiation resistance, frequent widespread disease, and a novel mechanism of MGMT regulation. Our data support the use of frontline TMZ in pediatric patients and underscore the importance of GTR when feasible.

Notably, combined treatment with an ACSS2 inhibitor and anti-PD1/L1 immunotherapy demonstrates superior synergistic efficacy in patient derived organoids and immunocompetent Rip1-Tag2 mice. This study delineates a non-redundant metabolic epigenetic barrier to chemotherapy and suggests that targeting the ACSS2/BCL6/P53 axis represents a promising strategy to overcome chemoresistance in PNET patients.

P2/3, N=447, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

P3, N=398, Not yet recruiting, NRG Oncology

P2, N=78, Recruiting, L. Nicolas Gonzalez Castro, MD, PhD | Trial completion date: Nov 2026 --> Mar 2027 | Trial primary completion date: Feb 2026 --> Aug 2026

This study delineates a complex spatial architecture of brain tissue with post-treatment changes and its discrepancies from progressive GB, thus facilitating future research into novel treatment strategies.

We demonstrate that CPZ, alone or in combination with temozolomide (TMZ), the current standard of care, activates the cGAS-STING signaling pathway, thus promoting anti-tumor immune responses. This study uncovers that CPZ exerts a previously unrecognized anti-cancer immunomodulatory activity, remodeling the immune microenvironment and enhancing the anti-tumor immune response. By overcoming TMZ resistance, CPZ not only exerts a direct anti-neoplastic effect, but also sensitizes GBM cells to standard therapy.

P=N/A, N=55, Recruiting, University College Cork | Trial completion date: Feb 2027 --> Dec 2027 | Trial primary completion date: Oct 2026 --> Jul 2027

P2/3, N=159, Completed, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Dec 2025 | Active, not recruiting --> Completed

P1/2, N=18, Recruiting, Cantex Pharmaceuticals | Not yet recruiting --> Recruiting

This study demonstrates that BET inhibition by JQ1 influences cellular sensitivity to TMZ and is associated with altered oxidative stress parameters and transcriptional reprogramming of epigenetic regulators in cervical cancer cells. While further protein-level and functional validation is required to establish causal mechanisms, these findings support the potential of BET-targeted strategies to modulate therapeutic responses in cervical cancer.