Abstract Library

#1163 Mitotane, Adrenolitic Drug, Inhibits Cell Survival and Function of Several Pituitary Cytotypes

Introduction: Mitotane (DDD) is an adrenolytic agent that is used for the treatment of adrenocortical carcinoma. We previously demonstrated that DDD affects thyrotrope cell viability and function. These data represent a possible explanation of the biochemical picture consistent with central hypothyroidism in patients undergoing DDD therapy. DDD also inhibits corticotrope cell viability by inducing caspase-mediated apoptosis and reduces POMC expression as well as basal and CRH-induced ACTH secretion. Cells originating from tissues different from pituitary are not sensitive to the inhibitory effects of DDD. Our data suggest that DDD inhibits cell survival and function of many pituitary cytotypes, acting with a generalized, but specific, toxic effect. The majority of male patients undergoing adjuvant DDD therapy show a clinical picture of hypogonadism, characterized by low free testosterone and unmodified LH concentration

Conference: 12th Annual ENETSConcerence (2015)

Presenting Author: Gentilin E

Authors: Gentilin E, Gagliano T, Benfini K, Di Pasquale C, Falletta S,

Keywords: mitotane, adrenocortical cancer, pituitary,

#66 Adrenocortical cancer: a therapeutic approach with everolimus (RAD001)

Introduction: Adrenocortical cancer (ACC) is a rare disease with very poor outcome. ACC responds poorly to standard chemotherapy. Mitotane, used as adjuvant therapy to surgery, prolongs recurrence-free survival, but the response is limited to 23% of patients and resistance occurs in the majority of patients (1). There is no curative therapy for ACC. Pre-clinical studies have shown involvement of both IGF-2/IGF-1R and Akt/mTOR pathways in ACC, and IGF-1R and mTOR inhibitors inhibited cell proliferation of human adrenocortical carcinoma cell lines in vitro (2,3,4).

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author:

Authors: Gueorguiev M, Bhattacharya S, Grossman A,

Keywords: adrenocortical cancer, mTOR inhibitors, everolimus,