PDF(Pubmed)
Abstract：
Repurposing anticancer drugs to vascular malformations has significantly improved patient outcomes. Complex Lymphatic Anomalies (CLA) are part of the spectrum of lymphatic malformations (LMs) that share similar oncogenic mutations to cancer. We report the case of a young patient with highly symptomatic CLA who was initially treated with sirolimus, due to the frequent involvement of the PI3K-AKT-mTOR pathway in CLA pathogenesis. Despite an initial reduction in symptoms, sirolimus progressively lost its effectiveness. After an unsuccessful attempt with trametinib alone, sirolimus was added to trametinib and resulted in a significant, rapid and sustained improvement in symptoms. This suggests that, contrary to current dogmas, combination therapy using sub-therapeutic doses targeting both the PI3K and RAS pathways retains efficacy without generating the toxicity known for combination therapies, and is beneficial in the management of CLAs and potentially other vascular anomalies.
摘要：
将抗癌药物重新用于血管畸形已经显著改善了患者的预后。复杂淋巴异常（CLA）是淋巴畸形（LM）的一部分，与癌症具有相似的致癌突变。我们报告了一个年轻的患者，有高度症状的CLA，最初接受西罗莫司治疗，由于PI3K-AKT-mTOR通路频繁参与CLA发病机制。尽管最初症状有所减轻，西罗莫司逐渐失去效力。在单独使用曲美替尼的尝试失败后，西罗莫司加入曲美替尼，症状快速持续改善。这表明,与目前的教条相反，使用针对PI3K和RAS途径的亚治疗剂量的联合疗法保留了疗效，而不会产生联合疗法已知的毒性，并且有益于CLA和潜在的其他血管异常的管理。
