It is well established that lipid metabolism is drastically altered during tumor development and response to therapy. Choline kinase alpha (ChoKα) is a key mediator of these changes, as it represents the first committed step in the Kennedy pathway of phosphatidylcholine biosynthesis and ChoKα expression is upregulated in many human cancers. ChoKα activity is associated with drug resistant, metastatic, and malignant phenotypes, and represents a robust biomarker and therapeutic target in cancer. Effective ChoKα inhibitors have been developed and have recently entered clinical trials. ChoKα's clinical relevance was, until recently, attributed solely to its production of second messenger intermediates of phospholipid synthesis. The recent discovery of a non-catalytic scaffolding function of ChoKα may link growth receptor signaling to lipid biogenesis and requires a reinterpretation of the design and validation of ChoKα inhibitors. Advances in positron emission tomography, magnetic resonance spectroscopy, and optical imaging methods now allow for a comprehensive understanding of ChoKα expression and activity in vivo. We will review the current understanding of ChoKα metabolism, its role in tumor biology and the development and validation of targeted therapies and companion diagnostics for this important regulatory enzyme. This comes at a critical time as ChoKα-targeting programs receive more clinical interest.

众所周知，在肿瘤发展和治疗反应过程中，脂质代谢会发生巨大变化。胆碱激酶 α (ChoKα) 是这些变化的关键介质，因为它代表了磷脂酰胆碱生物合成肯尼迪途径中的第一个关键步骤，并且 ChoKα 表达在许多人类癌症中上调。 ChoKα 活性与耐药性、转移性和恶性表型相关，是癌症中强有力的生物标志物和治疗靶点。有效的 ChoKα 抑制剂已经开发出来，并且最近进入了临床试验。直到最近，ChoKα 的临床意义还仅仅归因于它产生磷脂合成的第二信使中间体。最近发现 ChoKα 的非催化支架功能可能将生长受体信号传导与脂质生物发生联系起来，并且需要重新解释 ChoKα 抑制剂的设计和验证。正电子发射断层扫描、磁共振波谱和光学成像方法的进步现在可以全面了解 ChoKα 的体内表达和活性。我们将回顾目前对 ChoKα 代谢的理解、其在肿瘤生物学中的作用以及针对这种重要调节酶的靶向治疗和伴随诊断的开发和验证。这是一个关键时刻，因为 ChoKα 靶向项目受到了更多的临床关注。