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ETC-159, an Upstream Wnt inhibitor, Induces Tumour Necrosis via Modulation of Angiogenesis in Osteosarcoma

There is an increasing urgency in the search for new drugs to target high-grade cancers such as osteosarcomas (OS), as these have limited therapeutic options and poor prognostic outlook. Even though key molecular events leading to tumorigenesis are not well understood, it is widely agreed that OS tumours are Wnt-driven. ETC-159, a PORCN inhibitor that inhibits the extracellular secretion of Wnt, has recently progressed on to clinical trials. In vitro and in vivo murine and chick chorioallantoic membrane xenograft models were established to examine the effect of ETC-159 on OS. Consistent with our hypothesis, we noted that ETC-159 treatment not only resulted in markedly decreased β-catenin staining in xenografts, but also increased tumour necrosis and a significant reduction in vascularity-a hereby yet undescribed phenotype following ETC-159 treatment. Through further understanding the mechanism of this new window of vulnerability, therapies can be developed to potentiate and maximize the effectiveness of ETC-159, further increasing its clinical utility for the treatment of OS.

 

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The molecular events leading to osteosarcoma tumorigenesis are not yet fully understood, but it is widely believed that they are Wnt-driven. ETC-159 is a PORCN inhibitor that inhibits the extracellular secretion of Wnt, and it has recently progressed to clinical trials as a potential treatment for osteosarcomas.

To better understand the potential of ETC-159, in vitro and in vivo murine and chick chorioallantoic membrane xenograft models were established to examine its effect on osteosarcomas. The results showed that ETC-159 treatment resulted in significantly decreased β-catenin staining in xenografts, indicating inhibition of the Wnt pathway. Additionally, ETC-159 treatment led to increased tumour necrosis and a significant reduction in vascularity, which is a new and previously undescribed phenotype following ETC-159 treatment.

Further studies are needed to understand the mechanism underlying this new window of vulnerability, which may help develop new therapies to potentiate and maximize the effectiveness of ETC-159 in the treatment of osteosarcomas. Overall, this is an exciting development in the search for new treatments for high-grade cancers such as osteosarcomas.

Related Products

Cat.No. Product Name Information
S6616 ETC-159 ETC-159 (ETC-1922159) is an orally available, potent porcupine inhibitor with an IC50 of 2.9 nM for inhibiting β-catenin reporter activity in STF3A cells.

Related Targets

PORCN