Conventional chemotherapy and radiation induce more and more breast cancer stem cells (BCSC) resistance.

In recent years, increasing studies have suggested that the dysregulation of Wnt/β-catenin signaling occurs in breast cancer. A study from Gyu-Beom Jang, the researchers showed that the level of Wnt/β-catenin signaling in BCSC is relatively higher than in bulk tumor cells. Moreover, the results contribute to a relatively higher level of therapeutic resistance. They designed a highly potent selective Wnt/β-catenin signaling inhibitor, which antagonizes the binding of β-catenin to TCF in the nucleus. CWP232228 suppresses tumor formation and metastasis without toxicity through the inhibition of the growth of breast and liver cancer stem cells (CSCs).

Additionally, in Vitro, CWP232228 inhibits cell proliferation with IC50 values are 2 and 0.8 μM in mouse (4T1) and human MDA-MB-435 breast cancer cell lines, respectively. Additionally, CWP232228 0.01-10 μM; 48 hours inhibits cell proliferation with IC50s of 2.566, 2.630, and 2.596 μM in Hep3B, Huh7, and HepG2 cells, respectively.

Breast cancer usually metastasizes to multiple organs, primarily including the lungs, liver, and brain. Therefore, the scientists investigated the effect of CWP232228 on metastasis using breast cancer cell xenograft models. In vivo, CWP232228 resulted in a significant reduction in tumor volume. As a result, CWP232228 significantly reduced tumor bioluminescence in a fast-growing metastatic model of mouse breast cancer.

CWP232228 suppresses tumor formation and metastasis without toxicity through the inhibition of the growth of breast and liver cancer stem cells (CSCs).

To sum up, CWP232228 has the potential to be a potential clinical candidate for breast cancer treatment.

Reference:
Jang GB, et al. Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells. Cancer Res. 2015 Apr 15;75(8):1691-702.