Abstract：
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the standard of care for patients with advanced NSCLC and EGFR-sensitizing mutations. Both in osimertinib pivotal trials and in the post-marketing phase, asymptomatic creatinine phosphokinase elevation and clinically relevant muscle damage have been reported. However, the mechanisms underlying these conditions remain unclear. Herein, we report the first muscle biopsy description of osimertinib-induced myopathy and hypothesize that the mechanisms underpinning muscle toxicity could be driven by hyporegenerative mechanisms and mitochondrial dysfunction with subsequent reduced metabolic endurance, both directly linked to the inhibition of downstream molecular pathways mediated by EGFR in muscle cells.
摘要：
奥希替尼,第三代EGFR酪氨酸激酶抑制剂，是晚期NSCLC和EGFR致敏突变患者的治疗标准。在奥希替尼关键试验和上市后阶段，已报道无症状肌酐磷酸激酶升高和临床相关的肌肉损伤.然而,这些疾病的潜在机制尚不清楚.在这里，我们报告了奥希替尼诱导的肌病的首次肌肉活检描述，并假设支持肌肉毒性的机制可能是由再生机制和线粒体功能障碍引起的，随后代谢耐力降低。两者都与抑制肌肉细胞中EGFR介导的下游分子途径直接相关。
