HRD

P3, N=688, Not yet recruiting, Genmab

In addition, the combination therapy induces ferroptosis by inhibiting the Nrf2/SLC7A11/GPX4 axis, thereby exerting cytotoxic effects. Our results uncover a novel mechanism by which inhibiting DYRK1B enhances the anti-HGSOC efficacy of Niraparib and may offer a promising treatment strategy to improve the maintenance therapy in both HRD and HRP ovarian cancer patients.

Comprehensive genomic and transcriptomic profiling identified distinct molecular alteration patterns and therapeutic vulnerabilities among different classes of epithelial NENs from various tissues, warranting further investigation in anatomic-site-specific studies. Our outcome data underscore the clinical utility of broad molecular profiling in patients with advanced NENs lacking further standard treatment options.

Furthermore, baseline RB1 hemizygosity predicts inferior outcomes on CDK4/6i independent of germline status, supporting its role as a predictive biomarker. These findings have immediate clinical implications regarding the sequencing of PARPi and CDK4/6i in patients with gBRCA2 mutations and highlight a potential opportunity to anticipate and intercept resistance, leading to more durable clinical benefit.

In ER-positive, HER2-negative tumors from gBRCA1/2 carriers compared to noncarriers, we found significant enrichment of RB1 (OR:6.3;95%CI:2.8-15.4;padj = 0.001), TP53 (OR:4.6;95%CI:1.9-12.1;padj = 0.017), FAT1 (OR:3.9;95%CI:1.84-8.7;padj = 0.013), and MYC (OR:4.0;95%CI:1.8-9.1;padj = 0.017) SNV/indels/CNVs, associated with CDK4/6i resistance. Together, these findings demonstrate significant differences between gBRCA1 and gBRCA2-associated breast cancers, and preexisting CDK4/6i resistance mechanisms supporting prospective trials with individualized therapy for gBRCA1 vs gBRCA2 carriers, and comparing PARPi to CDK4/6i for ER-positive gBRCA1/2-associated breast cancer.

Integrating functional assessment of HRD and RS with immune contexture and considering these processes as outputs of their interconnected pathways in response to targeted agents could establish a unified therapeutic axis. Targeting this collective axis comprehensively may provide a promising foundation for next-generation, functionally guided treatment strategies capable of achieving durable responses with acceptable toxicity across diverse cancer types.

Adding maintenance olaparib to bevacizumab showed no clinically meaningful detrimental effect on global HRQoL either overall or in the HRD-positive subgroup. ClinicalTrials.gov ID: NCT02477644.

Sensitivity analysis across label definitions (scarHRD ≥ 33 and ≥ 42) showed robust performance, and a BRCA1/2 mutation-trained comparator performed near-randomly (AUC = 0.486), confirming that learned features reflect HRD biology beyond single-gene effects. IHGAMP supports a screening/triage role to prioritize confirmatory molecular testing where appropriate.

PFI, histological subtype, PS, and CA125 levels are important prognostic factors for the use of molecular-targeted agents for recurrent epithelial ovarian cancer. Patients with CC and EM subtypes experience worse outcomes than those with HGS, highlighting the need for subtype-specific management in recurrent ovarian cancer.

Overall, exceptional survival in HGSOC is associated with younger age, enrichment of BRCA2 mutations and BRCA1/RAD51C methylation, reduced CCNE1 amplification, and a competent antitumor immune response. These findings highlight potential biomarkers for refining risk stratification and guiding personalized therapeutic strategies in ovarian cancer management.

P=N/A, N=300, Recruiting, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of

P=N/A, N=0, The International Peace Maternity and Child Health Hospital of the China Welfare Institute; The International Peace Maternity and Child Health Hospita