Emerging strategies combining PARP inhibitors with PRMT, UBA1, WEE1, or MEK inhibitors are examined, alongside recent clinical trials including the GINECO study of bevacizumab, olaparib, and durvalumab. Current obstacles in resolving spatiotemporal PTM dynamics and cancer stem cell-specific vulnerabilities are outlined. This work aims to inform future research on targeting PARylation-associated PTM pathways to overcome ovarian cancer's evolvable resistance.

Mechanistically, CFB expression strongly correlated with PARP1 (R = 0.77), and CAF-derived CFB enhanced olaparib-induced DNA damage in TNBC models. Through integrative traditional and AI-driven approaches, this study supports CFB as a genetically associated risk protein with potential causal relevance and as a prognostic and therapeutic biomarker at both the expression and mutation levels in breast cancer. These findings provide a mechanistic and translational basis for precision therapy targeting CFB-overexpressing tumors.

P1, N=35, Enrolling by invitation, Brigham and Women's Hospital | Trial completion date: Mar 2026 --> Nov 2027 | Trial primary completion date: Mar 2025 --> Aug 2027

Additionally,TDG expression was positively associated with tumor mutational burden (P<0.001),microsatellite instability (P=0.045),mutant-allele tumor heterogeneity (P=0.001),and tumor neoantigens (P<0.001) in lung adenocarcinoma.In lung adenocarcinoma,the expression of TDG was notably elevated in the tumor tissue compared with that in adjacent normal tissue (P<0.001).Male patients exhibited higher levels of TDG expression than female patients (P=0.002),and smokers demonstrated higher TDG expression than non-smokers (P<0.001).Furthermore,TDG expression was correlated with smoking cessation duration (P=0.014).Positive correlations were observed for TDG expression with both clinical T stage (P=0.003) and distant metastasis (P=0.012),while a negative correlation was found with patient prognosis (P=0.030).Furthermore,TDG emerged as an independent prognostic factor for lung adenocarcinoma.In vitro experiments revealed that silencing TDG inhibited the proliferation and migration of lung adenocarcinoma cells (both P<0.05).A correlation analysis between TDG-related genes and target kinases revealed that in lung adenocarcinoma,genes encoding aurora kinase A,cyclin-dependent kinase 2 and other enzymes exhibited positive correlations with TDG expression (all P<0.001).Furthermore,TDG expression demonstrated positive correlations with functional states including the cell cycle,DNA damage,and DNA repair processes (all P<0.001).In addition,the expression of TDG was correlated with the efficacy of treatment in the first course in clinical patients (P=0.007).Specifically,TDG expression levels were higher in the progressive disease group than in the stable disease group (P=0.016),and lower in the complete remission group than in the progressive disease group (P<0.001).Additionally,elevated TDG expression was associated with enhanced resistance to oxaliplatin (P<0.001),carmustine (P<0.001),and olaparib (P=0.004). Conclusion TDG serves as a potential prognostic biomarker,an immunotherapeutic target,and a oncogene in pan-cancer,with particular significance in lung adenocarcinoma.

An equation based on five genes (ARID1A, NOTCH3, CSMD3, ELP4, and BARD1) showed strong predictive performance for olaparib response (area under the curve = 0.91). Collectively, these findings indicate that the CNV status of EV-DNA may serve as a non-invasive companion biomarker for patient stratification and therapeutic monitoring in HGSOC.

Particular emphasis is placed on the emerging role of natural products and compounds derived from traditional Chinese medicine, which exhibit promising preclinical activity in reversing resistance through modulation of efflux transporters, reactivation of apoptotic pathways, and inhibition of EMT. By integrating mechanistic understanding with novel therapeutic developments, this review provides a comprehensive outlook on strategies to enhance treatment durability and improve longterm clinical outcomes in TNBC.

This trial aims to provide high-quality evidence on whether a reduced number of chemotherapy cycles in the era of niraparib maintenance for 3 years can safely maintain efficacy while minimizing treatment-related toxicity and improving patients' quality of life.

Current FDA approved drugs and drugs in clinical trials targeted toward the genetic influences of breast cancer include those such as Talazoparib and Margetuximab. Additionally, risk assessment and genetic screening methods are incredibly important to inform patients of their individual risk for breast cancer development. Advancements in understanding of gene specific mechanism and their correlation with breast cancer pathogenesis may provide efficient strategies for precision medicine and enhancing clinical outcomes in breast cancer patients.

In patient-derived xenograft models harboring CDK12 alterations, combined PARP and ATR inhibition led to enhanced DSB accumulation and selectively suppressed tumor growth in CDK12-defective models. These findings highlight the importance of interrogating individual genes within the HRR pathway to define distinct mechanistic vulnerabilities and provide a strong rationale for combined PARP and ATR inhibition as a novel therapeutic strategy for patients with CDK12-altered prostate cancer.

P3, N=870, Active, not recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jul 2026 --> May 2027 | Trial completion date: Feb 2027 --> Jul 2029

P2, N=32, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Aug 2026

P=N/A, N=500, Not yet recruiting, Zhejiang Cancer Hospital