The challenge of developmental therapeutics for adrenocortical carcinoma

Oncotarget. 2016 Jul 19;7(29):46734-46749. doi: 10.18632/oncotarget.8774.


Adrenocortical carcinoma (ACC) is a rare disease with an estimated incidence of only 0.7 new cases per million per year. Approximately 30-70% of the patients present with advanced disease with very poor prognosis and without effective therapeutic options. In the recent years, unprecedented progresses in cancer biology and genomics have fostered the development of numerous targeted therapies for various malignancies. Immunotherapy has also transformed the treatment landscape of malignancies such as melanoma, among others. However, these advances have not brought meaningful benefits for patients with ACC. Extensive genomic analyses of ACC have revealed numerous signal transduction pathway aberrations (e.g., insulin growth factor receptor and Wnt/β-catenin pathways) that play a central role in pathophysiology. These molecular alterations have been explored as potential therapeutic targets for drug development. This manuscript summarizes recent discoveries in ACC biology, reviews the results of early clinical studies with targeted therapies, and provides the rationale for emerging treatment strategies such as immunotherapy.

Keywords: IGF-1R; VEGFR; adrenocortical carcinoma; targeted therapy; β-catenin.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / etiology
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / etiology
  • Humans
  • Molecular Targeted Therapy
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / physiology
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / physiology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / antagonists & inhibitors


  • TOR Serine-Threonine Kinases
  • Receptor, IGF Type 1
  • Receptors, Vascular Endothelial Growth Factor