Data from TAS0612, a Novel RSK, AKT, and S6K Inhibitor, Exhibits Antitumor Effects in Preclinical Tumor Models

• DOI: 10.1158/1535-7163.c.7054201.v1
• Publication Date: 2024-02-01T08:47:52Z
• Authors: Koji Ichikawa; Satoshi Ito; Emi Kato; Naomi Abe; Takumitsu Machida; Junya Iwasaki; Gotaro Tanaka; Hikari Araki; Kentaro Wakayama; Hideki Jona; Tetsuya Sugimoto; Kazutaka Miyadera; Shuichi Ohkubo

<div>Abstract<p>The MAPK and PI3K pathways are involved in cancer growth survival; however, the clinical efficacy of single inhibitors each pathway is limited or transient owing to resistance mechanisms, such as feedback signaling and/or reexpression receptor-type tyrosine kinases (RTK). This study identified a potent novel kinase inhibitor, TAS0612, characterized its properties. We found that TAS0612 potent, orally available compound can inhibit p90RSK (RSK), AKT, p70S6K (S6K) agent showed strong correlation with inhibition cells <i>PTEN</i> loss mutations, regardless presence <i>KRAS</i> <i>BRAF</i> mutations. Additional RSK inhibitory activity may differentiate sensitivity profile from target only pathway. Moreover, demonstrated broad-spectrum against tumor models wherein was insufficient exert antitumor effects. exhibited stronger growth-inhibitory cell lines dysregulated genetic abnormalities described above than treatment <i>AKT</i>, <i>PI3K</i>, <i>MEK</i>, <i>BRAF</i>, <i>EGFR/HER2</i>. In addition, persistence blockade downstream antiapoptotic signals, despite activation upstream effectors FoxO-dependent HER3. conclusion, RSK/AKT/S6K provide therapeutic strategy for patients improve responses overcome mechanisms.</p></div>