RAD51 (RAD51 Homolog A)

The CX3 complex-mediated R-loop resolution is independent of its fork maintenance function. Collectively, we demonstrate a previously unidentified role of the CX3 complex in preventing R-loop-induced genome instability by regulating FANCM-mediated R-loop resolution.

P2, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P2, N=27, Terminated, Leiden University Medical Center | N=55 --> 27 | Recruiting --> Terminated; recruitment was lower than expected (28/55) due to registration of the IMP in the first and second line treatment

We developed SeSA-HCPT, a dual-targeting compound that links the topoisomerase I inhibitor hydroxycamptothecin (HCPT) with a selenium analog of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid...In a PC-3 xenograft model, SeSA-HCPT significantly inhibited tumor growth relative to the combination treatment without observable systemic toxicity. These results nominate SeSA-HCPT as a promising dual-mechanism therapeutic candidate for advanced PCa.

This compound effectively inhibits RAD51-BRCA2 interaction, impairs homologous recombination, and synergizes with olaparib in BxPC-3 pancreatic cancer cells, inducing synthetic lethality in both 2D and 3D spheroids. Additionally, 19 showed efficacy in human pancreatic cancer cells and no toxicity in normal pancreatic cells, positioning it as an early tool compound and a starting point for further optimization.

P1, N=35, Recruiting, National Cancer Institute (NCI) | Active, not recruiting --> Recruiting

The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets.

In breast cancer models, elevated RAD51 succinylation correlates with reduced HR capacity and increased sensitivity to the PARP inhibitor olaparib, whereas diminished succinylation confers resistance. Moreover, a cell-penetrating peptide that disrupts the RAD51-HDAC11 interaction increases RAD51 succinylation and synergizes with chemotherapy. Collectively, our findings uncover a metabolic-epigenetic mechanism linking protein succinylation to HR and genomic stability and identify RAD51 succinylation as a predictive biomarker and therapeutic target in cancer.

In vivo, SZU305 showed strong antitumor activity without apparent toxicity, particularly when combined with sorafenib or irradiation in a Huh-7 xenograft model. These findings highlight the therapeutic potential of RAD51 degradation as a novel strategy to overcome drug resistance in liver cancer.

Cytogenetic analysis revealed inhibition of chromosome break repair and visible chromatin decondensation, suggesting that condensins function to maintain an appropriate chromatin state for efficient DSB repair in G2-phase. These results identify for the first time condensins as G2 phase-specific regulators of genome stability by fine-tuning HR and other resection-dependent DSB repair pathways.

This study elucidates the critical role and molecular mechanism through which KLF11 drives radiotherapy resistance in ESCC by regulating the MDM2/E2F1 axis and enhancing HR repair, thereby providing a solid theoretical foundation and potential target for the development of KLF11-targeted radiosensitization therapies for ESCC.

P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Dec 2029 | Trial primary completion date: Feb 2026 --> Dec 2029