NOTCH signaling dysregulation in ovarian cancer
The team from the Laboratory of Pharmacogenomics, Biomedical Center, has published a study in Biomedicine & Pharmacotherapy (Impact Factor 7.5; D1 – 95th percentile in Pharmacology & Pharmacy) investigating the effect of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response.
Analysis of tumor samples from 149 patients revealed significant upregulation of NOTCH1/3/4 and JAG2, with NOTCH2 being downregulated. Low NOTCH4 expression correlated with peritoneal metastasis and a shorter platinum-free interval, indicating its potential prognostic value.
Functional studies in cell lines and mouse models demonstrated that novel experimental “Stony Brook taxanes” effectively inhibited the growth of paclitaxel-resistant tumors and modulated NOTCH pathway genes, particularly NOTCH3. Knockdown of NOTCH3 increased the sensitivity of resistant cells to taxanes, highlighting it as a promising therapeutic target.
These findings confirm the crucial role of the NOTCH pathway in the development of chemoresistance and identify NOTCH3 as a potential target to improve therapy in patients with resistant ovarian cancer.
Koucka*, K., Spalenkova*, A., Seborova, K., Tesarova, T., Ehrlichova, M., Krus, I., … & Vaclavikova, R. (2025). Molecular impact of NOTCH signaling dysregulation on ovarian cancer progression, chemoresistance, and taxane response. Biomedicine & Pharmacotherapy, 191, 118532. doi.org/10.1016/j.biopha.2025.118532
TP53 and KRAS variability predicts prognosis and therapy response in epithelial ovarian carcinoma
In a second publication, in Cancer Biology & Therapy (Impact Factor 4.6; Q1 in Oncology), the team has described a comprehensive study that functionally validated somatic variants of TP53 and KRAS in 177 patients with epithelial ovarian carcinoma.
The analysis confirmed the high prevalence of TP53 mutations in high-grade serous carcinoma (HGSC), while KRAS mutations were enriched in non-HGSC subtypes and in earlier disease stages. TP53 variants disrupting the DNA-binding loop were associated with a longer platinum-free interval, whereas co-mutation of TP53–KRAS was linked to poorer overall survival in most cases. Intratumoral transcript levels of TP53 and KRAS significantly correlated with their respective protein levels and with each other, highlighting their functional impact.
These findings underscore the prognostic value of specific TP53 mutations and identify KRAS as a promising therapeutic target in non-HGSC tumors, supporting future clinical testing of KRAS inhibitors.
Allah, M.A.O., Ali E., Krus I., Holy P., Hanicinec V., Ambrozkiewicz F., … & Vaclavikova R. (2025). Functional validation of somatic variability in TP53 and KRAS for prediction of platinum sensitivity and prognosis in epithelial ovarian carcinoma patients. Cancer Biology & Therapy, 26(1), 2543105. DOI: 10.1080/15384047.2025.2543105
