The challenge of developmental therapeutics for adrenocortical carcinoma.
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.
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Ricardo
R
Costa
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Benedito A
BA
Carneiro
Department of Pathology, Messejana Heart and Lung Hospital, Fortaleza, Brazil.
Fabio
F
Tavora
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Sachin G
SG
Pai
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jason B
JB
Kaplan
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Young Kwang
YK
Chae
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Sunandana
S
Chandra
Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Peter A
PA
Kopp
Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.|Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Francis J
FJ
Giles
D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000209:etiology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D058990:Molecular Targeted Therapy; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
D017526:Receptor, IGF Type 1; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases
IGF-1R; VEGFR; adrenocortical carcinoma; targeted therapy; β-catenin