Cancer is a complex disease resulting from the interplay between the tumor cell and its microenvironment, featuring impaired apoptosis and activation of quiescent blood vessels to induce neovascularization to support metastasis. Two of the yet unmet needs in anticancer therapy are how to restore apoptosis and to abrogate metastatization.
We identified first-in-class OPA1 inhibitors with anti-cancer properties to overcome drug resistance, e.g., to Venetoclax and VEGF ligands, and thus treat cancer such as acute amyloid leukemia (AML) by specific induction of apoptosis and restriction of cancer angiogenesis.
OPA1 is mitochondrial dynamin like GTPase upregulated in several cancers where it prevents apoptosis, and its expression is correlated unfavorable prognosis. It is required for cancer angiogenesis and is responsible for Venetoclax resistance in AML.