Wnt/β-Catenin Inhibition by CWP232291 as a Novel Therapeutic Strategy in Ovarian Cancer

Abstract

The poor prognosis of ovarian cancer patients mainly results from a lack of early diagnosis approaches and a high rate of relapse. Only a very modest improvement has been made in ovarian cancer patient survival with traditional treatments. More targeted therapies precisely matching each patient are strongly needed. The aberrant activation of Wnt/β-catenin signaling pathway plays a fundamental role in cancer development and progression in various types of cancer including ovarian cancer. Recent insight into this pathway has revealed the potential of targeting Wnt/β-catenin in ovarian cancer treatment. This study aims to investigate the effect of CWP232291, a small molecular Wnt/β-catenin inhibitor on ovarian cancer progression. Various in vitro, in vivo and ex vivo models are established for CWP232291 testing. Results show that CWP232291 could significantly attenuate ovarian cancer growth through inhibition of β-catenin. Noticeably, CWP232291 could also s suppress the growth of cisplatin-resistant cell lines and ovarian cancer patient-derived organoids. Overall, this study has firstly demonstrated the anti-tumor effect of CWP232291 in ovarian cancer and proposed Wnt/β-catenin pathway inhibition as a novel therapeutic strategy against ovarian cancer.

Organoids in ovarian cancer: a platform for disease modeling, precision medicine, and drug assessment

“…PDOs have been widely used not only for high-throughput drug screening but also for validation of candidate drugs, novel biomarkers, or combination therapies that have already been proven effective in cell lines, as they provide highly individualized and faithful in vitro models, accelerating the clinical translation of new drug development and combination therapies while ensuring research quality (McDowell et al 2021 ; Vernon et al 2020 ; Wambecke et al 2021 ; Scattolin et al 2020 ; Granchi et al 2021 ; Liu et al 2022 ; Wang et al 2022a ; Wan et al 2022 ; Xuan et al 2022 ).…”

New Mechanisms for Anti-Cancer Drugs

“…FA is the most commonly used ligand for MOFs' surface functionalization to obtain FR-receptor targeting (Muhamad et al, 2018). In addition to active targeting, MOFbased nanocarriers utilizing intrinsic components of TME to generate ROS stress for a synergistic therapeutic effect along with chemotherapy present a new class of intelligent nanomaterials for efficient anticancer properties (Wang C. et al, 2022;Wang et al, 2022c;Liang et al, 2023). In this regard, bi-MIL-88B-FC can be effectively utilized as a potential DDS for multidimensional targeted chemotherapy and chemodynamic therapy based on mechanistic insights into the catalytic performance and drug release kinetics.…”

Research progress on the application of organoids in gynecological tumors

“…Wang et al extracted tissues from 20 patients with serous OC, cut them into small pieces, and incubated them in dispersed enzymes. Then, undigested tissue fragments were filtered and removed and embedded in a matrix gel growth factor-reduced basement membrane matrix without phenol red, ultimately forming OC-like organs ( Wang W. et al, 2022 ). Hoffmann et al obtained specimens from highly purified tumor deposits in the peritoneum or omentum of patients with HGSOC, inoculated in Matrigel matrix gel and supplemented with growth factor cultures to establish omental histologically derived organoids.…”