Researcher at National Cancer Institute (NCI) Publishes Research in Xenografts [Activity of the ubiquitin-activating enzyme inhibitor TAK-243 in adrenocortical carcinoma (ACC) cell lines, patient-derived organoids (PDOs) and murine xenografts].

A recent study conducted by researchers at the National Cancer Institute (NCI) has identified a potential new treatment option for metastatic adrenocortical carcinoma (ACC), a type of cancer that currently has limited treatment options. The study focused on the compound TAK-243, a clinical ubiquitin-activating enzyme E1 inhibitor, which showed potent activity in ACC cell lines. TAK-243 inhibited protein ubiquitination in ACC cells, leading to the accumulation of free ubiquitin, activation of the unfolded protein response (UPR), and induction of apoptosis. The researchers also found that TAK-243 had synergistic effects with current ACC therapies and BCL2 inhibitors in preclinical ACC models. These findings provide preclinical evidence to support the initiation of a clinical trial of TAK-243 in patients with advanced-stage ACC. [Extracted from the article]