预计到 2024 年，结直肠癌 (CRC) 将成为美国第三大确诊癌症和第三大致命癌症，其中早发性结直肠癌的发病率呈上升趋势。研究正在不断进行，以发现治疗各种癌症的新疗法，以改善患者的治疗结果和生存率。脂肪酸合酶（FAS）已成为治疗许多不同癌症的药物靶点。其中一种抑制剂 TVB-2640 因其对 FAS 的高度特异性而受到欢迎，并已进入治疗实体瘤的一期临床试验。然而，抑制 FAS 时发生的独特分子差异尚待了解。在这里，我们对用第 1 代（浅蓝素）或第 2 代（TVB-2640）FAS 抑制剂抑制的 HCT 116 和 HT-29 CRC 球体进行蛋白质组学和磷酸化蛋白质组学分析。参与脂质代谢和细胞呼吸的蛋白质发生大量改变。研究人员还观察到，参与铁死亡（铁介导的细胞死亡形式）的蛋白质发生了改变。这些结果表明，暴露于浅蓝素或 TVB-2640 的 HT-29 球体正在经历铁死亡机制。数据通过 PRIDE 存储库存入 ProteomeXchange 联盟，标识符为 PXD050987。

Colorectal cancer (CRC) is projected to become the third most diagnosed and third most fatal cancer in the United States by 2024, with early onset CRC on the rise. Research is constantly underway to discover novel therapeutics for the treatment of various cancers to improve patient outcomes and survival. Fatty acid synthase (FAS) has become a druggable target of interest for the treatment of many different cancers. One such inhibitor, TVB-2640, has gained popularity for its high specificity for FAS and has entered a phase 1 clinical trial for the treatment of solid tumors. However, the distinct molecular differences that occur upon inhibition of FAS have yet to be understood. Here, we conduct proteomics and phosphoproteomics analyses on HCT 116 and HT-29 CRC spheroids inhibited with either a generation 1 (cerulenin) or generation 2 (TVB-2640) FAS inhibitor. Proteins involved in lipid metabolism and cellular respiration were altered in abundance. It was also observed that proteins involved in ferroptosis─an iron mediated form of cell death─were altered. These results show that HT-29 spheroids exposed to cerulenin or TVB-2640 are undergoing a ferroptotic death mechanism. The data were deposited to the ProteomeXchange Consortium via the PRIDE repository with the identifier PXD050987.