title: Update on adrenocortical carcinoma management and future directions.
abstract: OBJECTIVE
  To present an update on the management of and future directions in adrenocortical carcinoma (ACC).
  
  
  RESULTS
  ACC is a rare malignancy with high morbidity and mortality. Surgery remains the mainstay treatment for localized disease, but it is often not feasible in more advanced cases. There is an ongoing controversy about the routine use of adjuvant treatments after surgery. Hormonal overproduction can complicate the management and worsen the prognosis of the disease. Systemic therapy with multiple cytotoxic drugs is often combined with the adrenolytic agent mitotane. Genomic analyses of ACC revealed numerous signal transduction pathway aberrations (insulin-like growth factor 2 overexpression, TP53 mutations and Wnt/β-catenin pathway activation), but so far, there has been no clinically meaningful breakthrough in targeting these genes. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in ACC is being explored in multiple ongoing trials.
  
  
  CONCLUSIONS
  Surgery by experienced team is the key treatment for localized ACC, whereas currently used chemotherapy has limited efficacy in advanced ACC. The improved understanding of the molecular pathways involved in ACC has not been translated into effective therapy. The development of new therapies requires collaborative effort to fight this disease.
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jeena
authors.initials: J
authors.lastname: Varghese
authors.forename: Mouhammed Amir
authors.initials: MA
authors.lastname: Habra
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D004704:Endocrinology / Q000639:trends*; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D008495:Medical Oncology / Q000639:trends*; D008939:Mitotane / Q000008:administration & dosage; D058990:Molecular Targeted Therapy / Q000379:methods; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D035703:Therapies, Investigational / Q000639:trends*
chemical_list: D008939:Mitotane