i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Cancer Signaling & Metabolism Group, IPATIMUP- Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Front Endocrinol (Lausanne). 2022 Jul 28;13:937367. doi: 10.3389/fendo.2022.937367. eCollection 2022.
Adrenal masses are one of the most common tumors in humans. The majority are benign and non-functioning and therefore do not require immediate treatment. In contrast, the rare adrenal malignant tumors are often highly aggressive and with poor prognosis. Besides usually being detected in advanced stages, often already with metastases, one of the reasons of the unfavorable outcome of the patients with adrenal cancer is the absence of effective treatments. Autophagy is one of the intracellular pathways targeted by several classes of chemotherapeutics. Mitotane, the most commonly used drug for the treatment of adrenocortical carcinoma, was recently shown to also modulate autophagy. Autophagy is a continuous programmed cellular process which culminates with the degradation of cellular organelles and proteins. However, being a dynamic mechanism, understanding the autophagic flux can be highly complex. The role of autophagy in cancer has been described paradoxically: initially described as a tumor pro-survival mechanism, different studies have been showing that it may result in other outcomes, namely in tumor cell death. In adrenal tumors, this dual role of autophagy has also been addressed in recent years. Studies reported both induction and inhibition of autophagy as a treatment strategy of adrenal malignancies. Importantly, most of these studies were performed using cell lines. Consequently clinical studies are still required. In this review, we describe what is known about the role of autophagy modulation in treatment of adrenal tumors. We will also highlight the aspects that need further evaluation to understand the paradoxical role of autophagy in adrenal tumors.
肾上腺肿瘤是人类最常见的肿瘤之一。大多数为良性和无功能性,因此不需要立即治疗。相比之下,罕见的肾上腺恶性肿瘤通常具有高度侵袭性和预后不良。除了通常在晚期被检测到,经常已经发生转移外,导致肾上腺癌患者预后不良的原因之一是缺乏有效的治疗方法。自噬是几种化疗药物靶向的细胞内途径之一。米托坦是治疗肾上腺皮质癌最常用的药物,最近被证明也能调节自噬。自噬是一个连续的程序化细胞过程,最终导致细胞细胞器和蛋白质的降解。然而,作为一个动态的机制,理解自噬流可能非常复杂。自噬在癌症中的作用被描述为自相矛盾的:最初被描述为肿瘤促进生存的机制,不同的研究表明,它可能导致其他结果,即肿瘤细胞死亡。在肾上腺肿瘤中,自噬的这种双重作用近年来也得到了研究。研究报告了自噬的诱导和抑制作为治疗肾上腺恶性肿瘤的一种策略。重要的是,这些研究中的大多数都是使用细胞系进行的。因此,仍然需要临床研究。在这篇综述中,我们描述了关于自噬调节在治疗肾上腺肿瘤中的作用的已知信息。我们还将强调需要进一步评估的方面,以了解自噬在肾上腺肿瘤中的矛盾作用。
Front Endocrinol (Lausanne). 2022
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