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Advanced Adrenocortical Carcinoma: Current Perspectives on Medical Treatment
Hormone and Metabolic Research ( IF 2.2 ) Pub Date : 2021-05-07 , DOI: 10.1055/a-1453-0806
Alexandra Novais Araújo 1 , Maria João Bugalho 1, 2
Affiliation  

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. For stage I and II tumors, surgery is a curative option, but even in these cases recurrence is frequent. Practical guidelines advocate a combination of mitotane with etoposide, doxorubicin, and cisplatin as first-line therapy for metastatic adrenocortical carcinoma. However, this scheme presents limited efficacy and high toxicity. The use of Immune Checkpoint Inhibitors (ICI) and multi-Tyrosine Kinase Inhibitors (mTKI) has modified the approach of multiple malignancies. The expectation of their applicability on advanced adrenocortical carcinoma is high but the role of these new therapies persists unclear. This article provides a short summary of last years’ findings targeting outcomes, limitations, and adverse effects of these new therapeutic approaches. The results of recent trials and case series pointed pembrolizumab as the most promising drug among these new therapies. It is the most often used ICI and the one presenting the best results with less related adverse effects when in comparison to the standard treatment with mitotane. Hereafter, the identification of specific molecular biomarkers or immune profiles associated with ICI or mTKI good response will facilitate the selection of candidates for these therapies. So far, microsatellite instability and Lynch Syndrome related germline mutations are suggested as predictive biomarkers of good response. Contrarywise, cortisol secretion has been associated with more aggressive ACC tumors and potentially poor responses to immunotherapy.

中文翻译:

晚期肾上腺皮质癌:医学治疗的当前观点

肾上腺皮质癌 (ACC) 是一种罕见的侵袭性恶性肿瘤。对于 I 期和 II 期肿瘤,手术是一种治疗选择,但即使在这些情况下,复发也很常见。实用指南提倡将米托坦与依托泊苷、多柔比星和顺铂联合作为转移性肾上腺皮质癌的一线治疗。然而,该方案表现出有限的功效和高毒性。免疫检查点抑制剂 (ICI) 和多酪氨酸激酶抑制剂 (mTKI) 的使用改变了多种恶性肿瘤的治疗方法。人们对其适用于晚期肾上腺皮质癌的期望很高,但这些新疗法的作用仍不清楚。本文简要总结了去年针对这些新治疗方法的结果、局限性和不良反应的发现。最近的试验和病例系列的结果表明,派姆单抗是这些新疗法中最有前途的药物。它是最常用的 ICI,与米托坦的标准治疗相比,它的效果最好,相关不良反应更少。此后,与 ICI 或 mTKI 良好反应相关的特定分子生物标志物或免疫特征的鉴定将有助于选择这些疗法的候选者。到目前为止,微卫星不稳定性和林奇综合征相关的种系突变被认为是良好反应的预测生物标志物。相反,皮质醇分泌与更具侵袭性的 ACC 肿瘤和对免疫治疗的潜在不良反应有关。它是最常用的 ICI,与米托坦的标准治疗相比,它的效果最好,相关不良反应更少。此后,与 ICI 或 mTKI 良好反应相关的特定分子生物标志物或免疫特征的鉴定将有助于选择这些疗法的候选者。到目前为止,微卫星不稳定性和林奇综合征相关的种系突变被认为是良好反应的预测生物标志物。相反,皮质醇分泌与更具侵袭性的 ACC 肿瘤和对免疫治疗的潜在不良反应有关。它是最常用的 ICI,与米托坦的标准治疗相比,它的效果最好,相关不良反应更少。此后,与 ICI 或 mTKI 良好反应相关的特定分子生物标志物或免疫特征的鉴定将有助于选择这些疗法的候选者。到目前为止,微卫星不稳定性和林奇综合征相关的种系突变被认为是良好反应的预测生物标志物。相反,皮质醇分泌与更具侵袭性的 ACC 肿瘤和对免疫治疗的潜在不良反应有关。与 ICI 或 mTKI 良好反应相关的特定分子生物标志物或免疫特征的鉴定将有助于选择这些疗法的候选者。到目前为止,微卫星不稳定性和林奇综合征相关的种系突变被认为是良好反应的预测生物标志物。相反,皮质醇分泌与更具侵袭性的 ACC 肿瘤和对免疫治疗的潜在不良反应有关。与 ICI 或 mTKI 良好反应相关的特定分子生物标志物或免疫特征的鉴定将有助于选择这些疗法的候选者。到目前为止,微卫星不稳定性和林奇综合征相关的种系突变被认为是良好反应的预测生物标志物。相反,皮质醇分泌与更具侵袭性的 ACC 肿瘤和对免疫治疗的潜在不良反应有关。
更新日期:2021-05-08
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