RAD51 (RAD51 Homolog A)

Consequently, SMG1i-induced cell death in splicing factor mutant leukemias could be further enhanced by inhibition of ATR or RAD51. This study shows that in vivo targeting of NMD is a therapeutic strategy to treat myeloid neoplasms with aberrant splicing.

Poorly differentiated endometrial carcinomas in Black South African women show a distinct MAPK-linked activation pattern, along with transcriptional repression and extensive splicing changes. Aligning with findings in African Americans, this cohort highlights the unique aspects of isoform-resolved splicing and zinc-finger repression, suggesting that translational control, retinoid signaling, and RNA processing may be targets for biomarkers and therapy.

Post-transcriptional regulation by 5-azacytidine (5-Aza) and synergy with doxorubicin (ADM) were assessed via DNA damage repair and apoptosis assays. AA@Tf-Lip enhanced cellular uptake and tumor specificity, achieving higher tumor inhibition and reduced cardiotoxicity versus free drugs. Indirect RDM1 inhibition via post-transcriptional regulation combined with targeted co-delivery effectively enhances HCC chemosensitivity, offering a safe, precise therapeutic strategy.

Critically, this process is dependent on the tumor suppressors BRCA1 and BRCA2 and is associated with the BRCA2-dependent accumulation of RAD51 recombinase in chromatin. Our data identify nascent strand gaps that are induced by olaparib independently of replication fork reversal and/or PRIMPOL-mediated repriming and that are repaired by a BRCA2-dependent process that we propose is daughter-strand gap protection and/or repair occurring hundreds of kilobases behind DNA replication forks.

These findings reveal a Cul4A-WDR5-dependent proteolysis pathway regulating HR protein stability via phosphatidyl inositol signaling. This mechanism offers a promising therapeutic strategy for overcoming PARPi resistance and improving combinatorial cancer treatment strategies.

GW833972A is effective by itself at high dose and can also be used at lower dosages to enhance the effectiveness of Poly (ADP-ribose) polymerase inhibitor (PARPi) treatments in BMAL2-expressing OCCC. Together, our findings reveal an essential oncogenic role of BMAL2 and demonstrate that it is an appealing therapeutic target, especially for ARID1A-wt OCCC.

Low BLM RNA expression is associated with improved survival after treatment with DNA-damaging agents, whereas low RAD51 expression shows a favorable but nonsignificant trend. These findings are exploratory and suggest that RNA-based HR gene expression may warrant further investigation as a potential prognostic biomarker in metastatic CRC.

In contrast, BRCA2-deficient cells showed a far greater defect in HRR and consistent sensitivity to both PARP-1 inhibitors, which was not enhanced by co-depletion of MCPH1. These data suggest that the magnitude of HRR defect in cancer cells influences PARP-1 inhibitor sensitivity and BRCA2 retains significant functionality in the absence of MCPH1.

miRNAs are crucial in BC treatment with PARP inhibitors. Further clinical studies are needed to validate their roles and develop miRNA-based strategies to overcome PARP inhibitor resistance.

ATR, AKT, and Notch inhibitors radiosensitize a preclinical model of ACC.

P2, N=88, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2026 --> Dec 2027

SANE-TZL markedly improves the delivery efficiency and antitumor activity of TZL in breast cancer models while maintaining a favorable safety profile. By combining a functional stearic acid carrier with TZL, this nanoemulsion formulation represents a safe and potent strategy to enhance PARP inhibitor-based chemotherapy in breast cancer, and it may provide a basis for further mechanistic studies on DNA damage response modulation.