De Martino Maria Cristina, Feelders Richard A, Pivonello Claudia, Simeoli Chiara, Papa Fortuna, Colao Annamaria, Pivonello Rosario, Hofland Leo J
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy.
Endocr Connect. 2019 Sep;8(9):R144-R156. doi: 10.1530/EC-19-0224.
Adrenocortical carcinomas (ACCs) are rare tumors with scant treatment options for which new treatments are required. The mTOR pathway mediates the intracellular signals of several growth factors, including the insulin-like growth factors (IGFs), and therefore represents a potential attractive pathway for the treatment of several malignancies including ACCs. Several mTOR inhibitors, including sirolimus, temsirolimus and everolimus, have been clinically developed. This review summarizes the results of the studies evaluating the expression of the mTOR pathway components in ACCs, the effects of the mTOR inhibitors alone or in combination with other drugs in preclinical models of ACCs and the early experience with the use of these compounds in the clinical setting. The mTOR pathway seems a potential target for treatment of patients with ACC, but further investigation is still required to define the potential role of mTOR inhibitors alone or in combination with other drugs in the treatment of ACC patients.
肾上腺皮质癌(ACC)是一种罕见的肿瘤,治疗选择有限,因此需要新的治疗方法。mTOR信号通路介导包括胰岛素样生长因子(IGF)在内的多种生长因子的细胞内信号,因此是包括ACC在内的多种恶性肿瘤治疗的潜在有吸引力的途径。包括西罗莫司、替西罗莫司和依维莫司在内的几种mTOR抑制剂已进入临床开发阶段。本综述总结了评估ACC中mTOR信号通路成分表达的研究结果、mTOR抑制剂单独或与其他药物联合在ACC临床前模型中的作用以及这些化合物在临床应用中的早期经验。mTOR信号通路似乎是ACC患者治疗的潜在靶点,但仍需要进一步研究来确定mTOR抑制剂单独或与其他药物联合在ACC患者治疗中的潜在作用。