Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.
Curr Opin Oncol. 2011 Jan;23(1):34-44. doi: 10.1097/CCO.0b013e328340d879.
Adrenocortical carcinoma is an aggressive, lethal malignancy of the adrenal cortex. The rarity of the disease has stymied therapeutic development. Recent work toward understanding the molecular pathogenesis of the disease has identified several potential new diagnostic and therapeutic targets.
The molecular characterization of adrenocortical carcinoma has identified dysregulation of the Gap 2/mitosis transition and the insulin-like growth factor 1 receptor signaling cascade as two major pathways for therapeutic development. These studies have also highlighted an unappreciated heterogeneity of the disease at the gene level that nevertheless seems to converge onto common cellular pathways. Additionally, the characterization of Wnt signaling through β-catenin in adrenal development, the demonstration of the involvement of BMP signaling in adrenocortical carcinoma growth regulation, and the discovery that ERCC1 expression levels can predict therapeutic response to platinum are just a few of the recent advances that promise to shed light on adrenocortical carcinoma biology.
Short-term, therapeutic development should target the Gap 2/mitosis transition and the downstream signaling of the insulin-like growth factor 1 receptor receptor. Long-term, additional characterization of patient samples, particularly at the sequence level, is required to fully understand adrenocortical carcinoma biology and apply that knowledge to clinical practice.
肾上腺皮质癌是一种侵袭性、致命性的肾上腺皮质恶性肿瘤。由于该病较为罕见，阻碍了治疗方法的发展。近期对其发病机制的分子研究确定了一些潜在的新的诊断和治疗靶点。
对肾上腺皮质癌的分子特征分析发现，GAP2/有丝分裂转换和胰岛素样生长因子 1 受体信号级联的失调是治疗开发的两个主要途径。这些研究还强调了该疾病在基因水平上存在未被充分认识的异质性，但似乎仍集中在共同的细胞途径上。此外，Wnt 信号通过β-连环蛋白在肾上腺发育中的作用、BMP 信号在肾上腺皮质癌生长调节中的作用以及 ERCC1 表达水平可以预测铂类治疗反应的发现，这些都是近期的进展，有望阐明肾上腺皮质癌的生物学特性。
短期内，治疗方法应针对 GAP2/有丝分裂转换和胰岛素样生长因子 1 受体受体的下游信号。从长远来看，需要对患者样本进行更多的特征分析，特别是在序列水平上，以充分了解肾上腺皮质癌的生物学特性，并将这些知识应用于临床实践。
