Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.
Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany; Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK.
Best Pract Res Clin Endocrinol Metab. 2020 May;34(3):101434. doi: 10.1016/j.beem.2020.101434. Epub 2020 Jun 18.
Almost one decade ago, etoposide, doxorubicin, cisplatin and mitotane (EDP-M) has been established as first-line systemic therapy of metastatic adrenocortical carcinoma (ACC). Although heterogeneous, the prognosis of advanced stage ACC is still poor and novel treatments are urgently needed. This article provides a short summary of current systemic ACC treatment and provides a comprehensive overview of new therapeutic approaches that have been investigated in the past years, including drugs targeting the IGF pathway, tyrosine kinase inhibitors, radionuclide treatment, and immunotherapy. The results of most of these trials were disappointing and we will discuss possible reasons why these drugs failed (e.g. drug interactions with mitotane, disease heterogeneity with exceptional responses in very few patients, and resistance mechanisms to immunotherapy). We then will present potential new drug targets that have emerged from many molecular studies (e.g. wnt/β-catenin, cyclin-dependent kinases, PARP1) that may be the foundation of next-generation therapies of ACC.
大约十年前，依托泊苷、多柔比星、顺铂和米托坦（EDP-M）已被确立为转移性肾上腺皮质癌（ACC）的一线全身治疗药物。尽管 ACC 具有异质性，但晚期 ACC 的预后仍然较差，迫切需要新的治疗方法。本文简要概述了目前的全身 ACC 治疗方法，并全面介绍了过去几年中研究过的新治疗方法，包括针对 IGF 途径的药物、酪氨酸激酶抑制剂、放射性核素治疗和免疫疗法。这些试验的大多数结果令人失望，我们将讨论这些药物失败的可能原因（例如，与米托坦的药物相互作用、疾病异质性导致极少数患者出现异常反应以及对免疫疗法的耐药机制）。然后，我们将介绍许多分子研究中出现的潜在新药物靶点（例如 Wnt/β-catenin、细胞周期蛋白依赖性激酶、PARP1），这些靶点可能成为下一代 ACC 治疗的基础。
