ETC-159 is a novel small molecule drug that targets a spread of cancers including colorectal, ovarian and pancreatic cancers. Its role is of an inhibitor in Wnt signalling pathways which promote cancer growth by allowing immune cells to access and enter the tumor. ETC-159 is been developed by partnership between .
ETC-159 inhibits an enzyme called porcupine, which prevents the secretion of Wnt proteins. ETC-159 is being tested in a clinical trial for use in cancers with overactive Wnt signalling, amongst other therapeutic indications during dose escalation in patients with advanced solid tumors; the utmost tolerated dose of ETC-159 is 30 mg every other day with dose-limiting toxicities and toxicity of concern of elevated serum b-CTX. ETC-159 with prophylactic denosumab is safe. ETC-159 has PD activity and increases immune infiltration. Currently ETC-159 dosing is ongoing at 24 mg.
The signal used for DNA repair helps to stop mutations from developing in stem cells residing inside the intestinal epithelium, further are often utilized in normal Wnt signalling in somatic cell maintenance.
Analysis of pre-clinical studies shows that the therapeutic doses of ETC-159 are well tolerated by the gut, without causing toxicity. This reflects that when a moment dose of ETC-159, given alongside PARP inhibitors, can prevent cancer resistance, while sparing intestinal stem cells, providing further options for treating cancers with hyperactive Wnt signalling.
The findings improve our understanding of how Wnt signalling enhances DNA repair in stem cells and cancers, maintaining their genomic integrity. Interventions that block Wnt signalling could cause some cancers and that they are often more sensitive to radiation and other DNA damaging agents.