Copyright: © 2026 Goetting et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Homologous recombination deficiency (HRD) is associated with response to poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer and can be assessed through BRCA1/2 loss-of-function alterations and overall genomic instability. HRD status was characterized in 58 ovarian cancer samples, primarily high-grade serous ovarian carcinoma (HGSC, n = 52), using the Oncomine™ Comprehensive Assay (OCA) Plus. HRD status was determined based on BRCA1/2 variants and a genomic instability metric (GIM) and compared with the FDA-approved gold standard method MyChoice® CDx assay. Overall, 33 samples (56.9%) were HRD-positive, including 53.4% of HGSC samples. BRCA1/2 mutations were detected in 11 samples (19.0%), with BRCA1 more frequently affected. Concordance between OCA Plus and MyChoice CDx assays was 91.4% for BRCA1/2 alterations, 83.3% for GIM, and 86.0% for HRD classification. Additional alterations of potential clinical relevance such as variants in homologous recombination repair genes, including ATM, PTEN, FANCE, and CDK12, CCNE1 amplifications, and TP53 mutations (86.2%) were detected. Loss of heterozygosity in BRCA1/2-mutated samples suggested potential biallelic loss-of-function. HRD-positive tumors, including both BRCA1/2-mutated and BRCA-wild type cases, showed significantly longer recurrence-free survival and apparent clinical benefit from PARPi treatment. This study supports the feasibility of in-house HRD assessment using comprehensive genomic profiling panels for precise molecular characterization.
Copyright: © 2026 Hopfgartner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Oncogenic signaling in cancer cells is essential for proliferation, and its disruption, either through inhibition or overactivation, can provide therapeutic opportunities. Dual specificity phosphatase 4 (DUSP4), a negative regulator of the MAPK pathway that dephosphorylates ERK, has been proposed as a potential target; however, its therapeutic relevance has not been evaluated in vivo. In this study, we show that DUSP4 knockdown induces G1 cell cycle arrest and reduces proliferation in BRAFV600E-mutant and BRAF inhibitor-resistant colorectal cancer models, both in vitro and in vivo, while also inducing a DUSP5-mediated adaptive response. While treatment achieved tumor stasis, indicating disease control, it did not yield tumor regression, suggesting that DUSP4 may have limited efficacy as a monotherapy target in cancer.
Copyright: © 2026 Brownlee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PURPOSE Thrombophilia genes contribute to tumorigenesis and thrombotic events in lung cancer, yet current treatments do not incorporate gene-specific strategies for F2, F5, PROS1, and SERPINC1. We evaluated survival in lung cancer patients with thrombophilia mutations. MATERIALS AND METHODS We queried TCGA-LUAD and TCGA-LUSC for primary lung cancers with F2, F5, PROS1, or SERPINC1 mutations. STAR RNA-seq expression was included in univariate and multivariate Cox models comparing patients with versus without thrombophilia mutations, adjusting for age, race, AJCC stage, primary site, treatment type, laterality, and treatment modalities. Hazard ratios with 95% confidence intervals were calculated. RESULTS We identified 569 patients with thrombophilia mutations and 850 without. Across all mutations, higher pathologic stage and right-sided tumors were associated with worse survival. F5 mutations were significantly associated with survival in middle-lobe (HR 1.49, p = 0.028), pleural (HR 1.33, p = 0.006), and upper-lobe (HR 1.20, p = 0.025) cancers. SERPINC1 and PROS1 mutations were associated with improved survival in upper-lobe cancers. Among upper-lobe cancers, African American patients with F5 mutations had worse survival by age at diagnosis (HR 1.01, p = 0.015) and race (HR 1.33, p = 0.024). CONCLUSIONS Thrombophilia mutations influence lung cancer survival and may help refine gene-targeted therapies.
