While there have been outstanding improvements in the treatment of Chronic Myeloid Leukaemia (CML), some patients do not respond optimally or are entirely resistant to treatment. In many of these patients, the molecular basis for resistance to tyrosine kinase inhibitors (TKIs) is unknown, highlighting the need for further investigation. Various potential mechanisms of TKI resistance are being explored with the aim of identifying new therapeutic options. A growing body of evidence suggests that alterations in lipid metabolism are implicated in treatment resistance in a variety of cancers including CML. Intracellular lipid storage may play a protective role to facilitate drug resistance in cancers and subsequently could serve as a targetable vulnerability. Due to the single genetic driver of oncogenesis, CML is an excellent model disease for studying metabolic alterations in cancer that contribute to drug resistance and disease progression. Based on the need to identify adjuvant therapies for TKI-resistant CML, we have evaluated evidence of dysregulated lipid storage in CML and its potential as a therapeutic target. In addition to in vitro analysis, we discuss the outcomes of clinical studies of CML treated with therapeutics that target lipid storage both directly and indirectly. We also highlight key limitations in the current literature and identify priority areas for further investigation. Advancing our understanding of lipid metabolic pathways, including lipid storage, in CML may reveal actionable vulnerabilities and support the development of novel therapeutic strategies to overcome TKI resistance.
尽管慢性髓系白血病（CML）的治疗已取得显著进展，但部分患者对治疗反应不佳或完全耐药。其中许多患者对酪氨酸激酶抑制剂（TKI）耐药的分子机制尚不明确，这凸显了进一步研究的必要性。目前学界正在探索TKI耐药的各种潜在机制，以期发现新的治疗策略。越来越多的证据表明，脂质代谢改变与包括CML在内的多种癌症的治疗耐药性相关。细胞内脂质储存可能通过发挥保护作用促进癌症耐药，进而成为可靶向的治疗突破口。由于CML的癌变过程由单一遗传驱动因素主导，使其成为研究癌症代谢改变如何导致耐药及疾病进展的理想模型疾病。基于对TKI耐药性CML辅助疗法的需求，我们评估了CML中脂质储存失调的证据及其作为治疗靶点的潜力。除体外分析外，我们还讨论了直接或间接靶向脂质储存的CML临床治疗研究结果。同时，我们指出了当前文献中的关键局限性，并明确了未来研究的重点方向。深化对CML脂质代谢途径（包括脂质储存）的理解，可能揭示可干预的薄弱环节，并为开发克服TKI耐药的新型治疗策略提供支持。
肿瘤(癌症)患者之家