复发/转移性腺样囊性癌（ACC）是一种罕见的、无法治愈的疾病。 MYB 是 ACC 中假定的致癌驱动因素，通常通过 MYB-NFIB 重排过度表达。作者假设，变构抑制剂 MK-2206 抑制 AKT 可以降低无法治愈的 ACC 患者的 MYB 表达并诱导肿瘤消退（ClinicalTrials.gov 标识符 NCT01604772）。患有进行性、无法治愈的 ACC 患者入组并每周接受 MK-2206 150 毫克治疗;允许增加至 200 毫克。主要终点是确认的反应。次要终点是无进展生存期、总生存期和安全性。在一组患者中进行了一项探索性分析，评估 MK-2206 对 MYB 表达的影响。纳入了 16 名患者，其中 14 名可评估疗效。没有观察到确认的反应。 13 名患者病情稳定，1 名患者的最佳反应是疾病进展。中位无进展生存期为 9.7 个月（95% CI，3.8-11.8 个月），中位总生存期为 18.0 个月（95% CI，11.8-29.9 个月）。 16 名患者中有 9 名 (56%) 出现至少一项 3 级治疗相关不良事件，最常见的是皮疹 (38%)、疲劳 (19%)、淋巴细胞计数减少 (13%) 和高血糖 (13%) ）。 14 个肿瘤中有 12 个（86%）通过免疫组织化学可检测到 MYB 表达，14 个肿瘤中有 7 个（50%）有 MYB-NFIB 基因重排。连续活检显示，MK-2206 治疗后，五名患者中有四名的 MYB 水平降低。MK-2206 未能在无法治愈的 ACC 患者中诱导临床反应。 AKT 抑制可能会降低 MYB 蛋白水平，但效果在患者之间差异很大。需要针对 ACC 中的 MYB 的新方法。© 2023 美国癌症协会。

Recurrent/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed through an MYB-NFIB rearrangement. The authors hypothesized that AKT inhibition with the allosteric inhibitor MK-2206 could decrease MYB expression and induce tumor regression in patients with incurable ACC (ClinicalTrials.gov identifier NCT01604772).Patients with progressive, incurable ACC were enrolled and received MK-2206 150 mg weekly; escalation to 200 mg was allowed. The primary end point was confirmed response. Secondary end points were progression-free survival, overall survival, and safety. An exploratory analysis evaluating the effect of MK-2206 on MYB expression was conducted in a subset of patients.Sixteen patients were enrolled, and 14 were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease, and one had disease progression as their best response. The median progression-free survival was 9.7 months (95% CI, 3.8-11.8 months), and the median overall survival was 18.0 months (95% CI, 11.8-29.9 months). Nine of 16 patients (56%) had at least one grade 3 treatment-related adverse event, and the most common were rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) had detectable MYB expression by immunohistochemistry, and seven of 14 tumors (50%) had an MYB-NFIB gene rearrangement. Serial biopsies revealed decreased MYB levels with MK-2206 in four of five patients.MK-2206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, although the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed.© 2023 American Cancer Society.