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.

Purpose Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in Korea. It is also the third most frequently diagnosed malignancy worldwide. To significantly improve its oncologic outcome, there is a need to study the diagnosis and treatment strategies further. Methods We established 21 patients-derived organoids from 20 patients with CRC, and characterized their cellular and molecular features. Whole exome sequencing (WES) was performed for these organoids to obtain mutational profiles. It generally took 3 ~ 4 weeks for organoids to grow enough for DNA/RNA extraction and drug screening. The research protocol was reviewed and approved by the institutional review board of the Seoul National University Hospital (IRB No. 1102-098-357). Results Single nucleotide variations, in-frame deletions and insertions, and splice site mutations of CRC related genes were found and classified based on their existing pathogenicity reports from National Center for Biotechnology Information (NCBI). Heterogeneity was confirmed by comparing the expression of each organoid in the major cancer pathway through RNA sequencing. Also, drug sensitivity assay was performed to measure cell viability after treatment with 24 anti-cancer drugs approved by FDA. Conclusion We used the organoid model to identify tumor heterogeneity through various screening. By integrating mutational profiles of WES, RNA-seq, and drug screening results, we could elucidate which mechanism went wrong. Results suggested that tumor heterogeneity should be considered when using organoids as a preclinical model and that organoids are a suitable platform for use in precision medicine. Organoid model is meaningful because we can figure out what therapy will be good for a patient in vitro in a few weeks so that clinical application can be suggested.