Ovarian Cancer

Combination treatment with a VEGF inhibitor rescued cytotoxicity in hypoxia-conditioned ovarian cancer cell lines with preserved target antigen expression. Collectively, these data outline a link between hypoxia and the development of resistance to BITEs and posits inhibition of VEGF inhibition as a potentially important therapeutic intervention.

Our results indicate that BRCA2 c.8351G>A p.(Arg2784Gln) has a disease-causing effect, with reduced penetrance, similar to other pathogenic variants in moderate risk breast cancer genes such as ATM and CHEK2. We also provide risk-adapted recommendations for clinical management. Importantly, one should be aware of a reduced penetrance as the underlying reason for conflicting results among pieces of evidence used for variant classification.

Elevated C/EBPβ expression enhanced cisplatin resistance and olaparib resistance. Targeting C/EBPβ via CDK12 inhibition could rescue drug responsiveness of ovarian cancer, thereby counteracting platinum and PARP inhibitor resistance. C/EBPβ could thus be exploited as a candidate prognostic biomarker in ovarian cancer.

Attenuating peripheral serotonin using fluoxetine-a selective serotonin reuptake inhibitor (SSRI) antidepressant-ablates TAM-derived EV delivering of inositol metabolic enzymes and sensitizes tumors to cisplatin/PARP inhibitor (PARPi). Our study unveils a systemic serotonin-primed metabolic crosstalk within the tumor microenvironment that potentiates chemoresistance, revealing targetable HR repair regulation beyond cancer-cell-autonomous mechanisms.

P=N/A, N=300, Not yet recruiting, Colorado State University

P1/2, N=292, Active, not recruiting, ImCheck Therapeutics | Trial completion date: Dec 2025 --> Oct 2026 | Trial primary completion date: Sep 2025 --> Oct 2026

FOLR1 is overexpressed in a large percentage of low-grade serous ovarian cancers. Mirvetuximab soravtansine may represent a novel treatment option for low-grade serous ovarian cancer patients progressing after standard treatment modalities. Clinical trials with mirvetuximab soravtansine in FOLR1-positive low-grade serous ovarian cancers are warranted.

Tumor invasion was associated with the activation of interferon response pathways, epithelial-mesenchymal transition, and extracellular matrix remodeling. In summary, these results elucidate the earliest molecular landscape of ovarian precancerous lesions, serving as the foundation for future risk stratification to identify aggressive pre-cancerous lesions.

Multivariate analysis confirmed that both advanced FIGO stage and loss of SMARCA4 were independent adverse prognostic factors. This study demonstrates the clinical utility of SWI/SNF complex evaluation, wherein SMARCA4 loss specifically pinpoints an aggressive tumor subset, providing a crucial tool for risk stratification.

The impact of SLC44A4 on the extracellular matrix and PI3K/Akt signaling pathway was evaluated by Western blotting.SLC44A4 inhibited the proliferation and migration of OCCC cells in vitro, altered the extracellular matrix, and may inhibit the PI3K/Akt signaling pathway.SLC44A4 overexpression can alter the tumor microenvironment and inhibit the malignant progression of ovarian clear cell carcinoma (OCCC) by remodeling its extracellular matrix. These findings suggest that SLC44A4 may serve as a potential biomarker for evaluating the prognosis of OCCC.

These findings raise the hypothesis of a potential association between PM and GU malignancy. Shared origins, oncogenesis of similar cell types, environmental exposures or genetic predispositions may contribute and warrant further investigation.