The Developmental Pathway (Hh/Wnt) Set comprises approximately 2,000 compounds that target the developmental proteins Hedgehog (Hh) and Wnt. These proteins are crucial regulators of cell fate, differentiation, and proliferation. The Hh-signaling pathway is complex and features several regulatory proteins that, when activated, encourage the transcription of target genes responsible for cellular growth and differentiation during embryonic development. Dysregulation of the Hh-signaling pathway can cause various types of human malignancy.
Similarly, the Wnt-signaling pathway plays a vital role in physiologic processes such as embryonic development, proliferation, and differentiation while also participating in the development and progression of many types of malignancies. Activation of the canonical Wnt/β-catenin signaling pathway causes the accumulation of β-catenin in the nucleus, promoting the expression of target genes. Conversely, the inactivation of the Wnt signaling pathway is the norm.
It is worth mentioning that there exists crosstalk between the Wnt/β-catenin and the Hh-signaling pathways. The Developmental Pathway (Hh/Wnt) Set offers a potential resource for developing anticancer drugs that target these pathways. Inhibitors of the Hh/Wnt pathways have already shown their efficacy in preclinical assays by inducing tumor regression. For instance, well-known inhibitors like cyclopamine target the Hh/Wnt receptor complexes.
Overall, the Developmental Pathway (Hh/Wnt) Set is potentially useful for studying the regulation of the Hh-signaling and Wnt-signaling pathways, which could eventually lead to the discovery of therapeutic agents to address malignancies caused by dysregulation of these pathways.
