YAP/TAZ inhibitors for cancer.

OVERVIEW

Georgetown University researchers discovered a potential drug treatment method whereby the YAP/TAZ pathway is inhibited in NF2-mutant cancer cells to impede glycolysis and force mitochondrial respiration, leading to mitochondrial dysfunction, oxidative stress, and tumor shrinkage. This method includes the potential for MAPK inhibitor co-administration as a means to counteract YAP/TAZ inhibitor resistance.

BACKGROUND

The NF2 gene encodes for the tumor suppressor protein Merlin, which is responsible for the regulation of several key cell signaling pathways. One such pathway is the homeostasis-regulating Hippo pathway, in which the transcriptional co-activators yes-associated protein 1 (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are usually deactivated. In NF2-mutant cells, YAP/TAZ activation can cause cancer-inducing changes to gene expression. Therefore, solutions with the ability to inhibit YAP/TAZ could prove helpful in treating NF2-mutant tumors in patients.

Benefit

• Novel cancer treatment method targeting the Hippo-YAP/TAZ pathway.
• Safer than other common anti-cancer drug treatment methods.

Market Application

• Treatment or prevention of cancer, noncancerous tumors, or lesions through the administration of one or more inhibitors of the YAP/TAZ pathway.

Publications

• US patent No. 17/608,981
• YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells (DOI: 10.1016/j.devcel.2019.04.014) (link: https://pubmed.ncbi.nlm.nih.gov/31063758/)
• Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma (DOI: 10.1158/1535-7163.MCT-20-0717) (link:https://aacrjournals.org/mct/article/20/6/986/673270/Small-Molecule-Inhibitors-of-TEAD-Auto)