Potential Effects of Ketoconazole on ACTH-Producing and Non-ACTH-Producing Neuroendocrine Tumors

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Introduction: Prolonged biochemical remission after treatment with steroidogenesis inhibitors has been described in patients with Cushing’s syndrome due to ectopic adrenocorticotropin hormone (ACTH) production. Some studies have suggested antiproliferative and apoptotic effect of ketoconazole in human cancer cells.

Aim(s): Based on this, we explored the putative effect of ketoconazole on ACTH-producing and non-ACTH producing neuroendocrine tumor cell lines and its combination with somatostatin analogs.

Materials and methods: Cultures of human ectopic ACTH-producing small cell lung carcinoma (DMS-79) and BON-1 pancreatic NET cells were used. Total cell number, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC), somatostatin receptor subtype (sst) expression by qRT-PCR, as well as serotonin-, CgA- and ACTH secretion were assesed. Effects of ketoconazole alone and in combination with octreotide and pasireotide were evaluated.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Herrera-Martínez A

Authors: Herrera-Martínez A, Feelders R, Castaño J, Van Dungen R, Dogan-Oruc F,

Keywords: ACTH- and non-ACTH producing NETs, ketoconazole, somatostatin analogs, apoptosis, cytotoxicity,