ATR (Ataxia telangiectasia and Rad3-related protein)

Ceralasertib monotherapy was generally well tolerated in Japanese patients with advanced solid tumors. The small number of patients enrolled prevents definitive conclusions on the efficacy of ceralasertib monotherapy to be made.

Sirtinol was detected in the brains of sirtinol-treated mice, suggesting blood brain barrier penetrance. Conclusions : Based on our results, sirtinol shows promise as a selective, redox-modulating therapeutic for DIPG that enhances oxidative stress and interferes with DNA repair.

The challenges that must be addressed to see the true potential of these agents are discussed. Finally, we consider future directions and the necessity for integration of biomarkers and genomic profiling in DDR inhibitor clinical trials to optimally identify patients with tumours genetically vulnerable, and so crucially, take advantage of the selective therapeutic opportunity provided by DDR inhibition.

This resistance is suppressed by exogenously transfected miR-181d. These findings suggest that microRNA regulates intratumoral heterogeneity by modulating the transcriptional variability of key DNA repair enzymes, providing a compelling rationale for miRNA delivery as a platform for glioblastoma therapy.

Deletion of MLH1 sensitized esophageal cancer cells to novobiocin. MLH1 plays important roles in DSB repair and deletion of MLH1 sensitizes ESCC cells to Polθ inhibitor.

Berzosertib 270 mg/m2 and irinotecan 180 mg/m2 was the RP2D. The combination is associated with manageable side effects and promising disease activity in ATM mutant solid tumors.

The aim of this study is to explore the role of C1orf116 in the development of acquired resistance to erlotinib in LUAD...Low expression of C1orf116 enhances the DNA damage response and promotes resistance to EGFR inhibitors in LUAD. This discovery suggests a potential therapeutic approach to combat acquired resistance through targeting the ATM/ATR signaling pathway.

Cisplatin combined with elimusertib was associated with hematologic toxicity requiring significant dose de-escalation. Elimusertib PK was consistent with prior studies. Only modest activity was observed. Further clinical evaluation of elimusertib plus cisplatin is not warranted.

Flow cytometry analysis revealed that Orox A treatment caused G2/M phase arrest in the cell cycle. These findings collectively suggest that Orox A exerts cytotoxic effects on Hep3B cells through mechanisms involving DNA damage, oxidative stress, and cell cycle modulation, making it a promising candidate for further anticancer therapy development.

Using atomic force microscopy, we found that nuclear actin assembly or nuclear DIAPH3 activity promotes nuclear stiffness in an ATR-dependent manner. Thus, our study identifies an ATR-formin module that regulates nuclear mechanical properties through induction of intranuclear actin scaffolding.

At the same time, compound 15 is confirmed to inhibit doxorubicin- but not UV-induced DNA damage response via the ATR/Chk1 signaling pathway. The hybrids show lower IC50 values compared to the fragments alone, highlighting the potential for using hybrid molecules containing two pharmacophores with complementary activities. These results suggest that novel hybrid molecules may serve as new leads against multiple myeloma.

Gemcitabine induces nuclear cGAS accumulation independent of STING-mediated immune activation. The binding of nuclear cGAS to γH2AX at double strand DNA breaks (DSBs) plays a pivotal role in RS activation and mitotic catastrophe in gemcitabine and AZD6738 treated cells.