The next step: mechanisms driving adrenocortical carcinoma metastasis

Abstract

Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

“…Despite the recent insights into the molecular characterization of ACC, the mechanisms underlying tumor progression and aggressiveness still need to be elucidated [31]. Accordingly, any modern approach can no longer focus on tumor cells alone and therefore we directed our study to include the plastic interacting network of the surrounding adipose microenvironment.…”

Establishing a human adrenocortical carcinoma (ACC)-specific gene mutation signature

“…ACC has a high risk of metastatization even after early diagnosis and surgery [4] . Metastasis is the ability of tumor cells to leave the primary site and migrate to other tissues, leading to the spread of cancer throughout the body [5] . The molecular mechanisms of metastasis have been well-studied in carcinomas, in which epithelial to mesenchymal transition (EMT) is considered a critical process [5,6] .…”

“…Metastasis is the ability of tumor cells to leave the primary site and migrate to other tissues, leading to the spread of cancer throughout the body [5] . The molecular mechanisms of metastasis have been well-studied in carcinomas, in which epithelial to mesenchymal transition (EMT) is considered a critical process [5,6] . Invasion could either occur through the lymphatic system, through the venous system or through the extra-adrenal tissues [7] .…”

“…Invasion could either occur through the lymphatic system, through the venous system or through the extra-adrenal tissues [7] . Tissue biopsy is unhelpful and tumor protein p53 (TP53) expression appeared to be inadequate as prognostic marker in ACC; instead, quantification of cell proliferation marker MKI67 is critical for prognosis also in ACC [1,5,8,9] . Several genes have been proposed as cancer drivers in ACC, amongst them: TP53 and catenin β 1 (CTNNB1) [10][11][12] .…”

Pathobiology and genetics of adrenocortical carcinoma

“…In addition to Ki67, there has been a lot of interest in defining new immunohistochemical markers to aid in the prognosis of ACC (reviewed in Lalli & Luconi 2018).…”