The Hedgehog signaling pathway is a target of growing interest in the oncology community. It represents a new way of understanding and potentially attacking the progression and reoccurrence of cancer. The Hedgehog pathway is normally active during embryonic development and regulates tissue and organ formation. When abnormally activated in adults, the Hedgehog pathway is believed to play a central role in allowing the proliferation and survival of cancer cells.

The role of the Hedgehog pathway in cancer is believed now to be implicated in three distinct manifestations. The first is in cancers where there is a genetic mutation in which the pathway is constitutively active, such as medulloblastoma and basal cell carcinoma. The second is in cancers in which the pathway is aberrantly expressed and the pathway is activated, such as pancreatic cancer and prostate cancer. Finally, there is a growing body of evidence suggesting the Hedgehog pathway’s role in cancers in which there is a subset of tumor progenitor cells believed to have greater self-renewal capacity. These cells are suspected to be responsible for disease relapse following treatment with conventional therapeutic agents such as small cell lung cancer and glioblastoma.

Infinity has developed a novel, proprietary Hedgehog pathway inhibitor,
IPI-926. In preclinical models, IPI-926 has shown potent and selective inhibition of the Hedgehog pathway, anti-tumor activity, and attractive pharmacologic properties, including oral bioavailability and favorable half-life.

Hedgehog Structure and Function Hedgehog Inhibition