{"id":4392,"date":"2025-09-23T17:17:40","date_gmt":"2025-09-23T15:17:40","guid":{"rendered":"https:\/\/biomedic.lfp.cuni.cz\/?p=4392"},"modified":"2025-09-23T17:28:58","modified_gmt":"2025-09-23T15:28:58","slug":"two-new-studies-from-laboratory-of-pharmacogenomics-investigate-ovarian-cancer","status":"publish","type":"post","link":"https:\/\/biomedic.lfp.cuni.cz\/en\/pharmacogenomics-laboratory\/two-new-studies-from-laboratory-of-pharmacogenomics-investigate-ovarian-cancer\/","title":{"rendered":"Two new studies from Laboratory of Pharmacogenomics investigate ovarian cancer"},"content":{"rendered":"\n\n\n\n\n

NOTCH signaling dysregulation in ovarian cancer<\/strong><\/strong><\/p>\n\n\n\n

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.<\/p>\n\n\n\n

Analysis of tumor samples from 149 patients revealed significant upregulation of NOTCH1\/3\/4 <\/em>and JAG2<\/em>, with NOTCH2<\/em> being downregulated. Low NOTCH4 expression correlated with peritoneal metastasis and a shorter platinum-free interval, indicating its potential prognostic value.<\/p>\n\n\n\n

Functional studies in cell lines and mouse models demonstrated that novel experimental \u201cStony Brook taxanes\u201d effectively inhibited the growth of paclitaxel-resistant tumors and modulated NOTCH pathway genes, particularly NOTCH3<\/em>. Knockdown of NOTCH3<\/em> increased the sensitivity of resistant cells to taxanes, highlighting it as a promising therapeutic target.<\/p>\n\n\n\n

These findings confirm the crucial role of the NOTCH pathway in the development of chemoresistance and identify NOTCH3 <\/em>as a potential target to improve therapy in patients with resistant ovarian cancer.<\/p>\n\n\n\n

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<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

TP53 and KRAS variability predicts prognosis and therapy response in epithelial ovarian carcinoma<\/strong><\/strong><\/p>\n\n\n\n

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<\/em> and KRAS<\/em> in 177 patients with epithelial ovarian carcinoma.<\/p>\n\n\n\n

The analysis confirmed the high prevalence of TP53<\/em> mutations in high-grade serous carcinoma (HGSC), while KRAS<\/em> mutations were enriched in non-HGSC subtypes and in earlier disease stages. TP53<\/em> variants disrupting the DNA-binding loop were associated with a longer platinum-free interval, whereas co-mutation of TP53\u2013KRAS<\/em> was linked to poorer overall survival in most cases. Intratumoral transcript levels of TP53<\/em> and KRAS<\/em> significantly correlated with their respective protein levels and with each other, highlighting their functional impact.<\/p>\n\n\n\n

These findings underscore the prognostic value of specific TP53<\/em> mutations and identify KRAS<\/em> as a promising therapeutic target in non-HGSC tumors, supporting future clinical testing of KRAS<\/em> inhibitors.<\/p>\n\n\n\n

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<\/p>\n\n\n\n

\"\"<\/figure>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":58,"featured_media":4391,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"wds_primary_category":0,"footnotes":""},"categories":[151,123,152,119,153],"tags":[149,154,155],"coauthors":[135],"class_list":["post-4392","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-aktuality-en","category-homepage","category-laborator-farmakogenomiky-en","category-pharmacogenomics-laboratory","category-vybrane-en","tag-oncology","tag-onkologie-en","tag-publikace-en"],"acf":[],"_links":{"self":[{"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/posts\/4392","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/users\/58"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/comments?post=4392"}],"version-history":[{"count":9,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/posts\/4392\/revisions"}],"predecessor-version":[{"id":4407,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/posts\/4392\/revisions\/4407"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/media\/4391"}],"wp:attachment":[{"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/media?parent=4392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/categories?post=4392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/tags?post=4392"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/biomedic.lfp.cuni.cz\/en\/wp-json\/wp\/v2\/coauthors?post=4392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}