Reviews:
The challenge of developmental therapeutics for adrenocortical carcinoma
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Abstract
Ricardo Costa1,2, Benedito A. Carneiro1,2, Fabio Tavora4, Sachin G. Pai1,2, Jason B. Kaplan1,2, Young Kwang Chae1,2, Sunandana Chandra1,2, Peter A. Kopp3 and Francis J. Giles1,2
1 Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
2 Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
3 Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
4 Department of Pathology, Messejana Heart and Lung Hospital, Fortaleza, Brazil
Correspondence to:
Ricardo Costa, email:
Keywords: adrenocortical carcinoma, targeted therapy, IGF-1R, β-catenin, VEGFR
Received: March 02, 2016 Accepted: April 10, 2016 Published: April 18, 2016
Abstract
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.
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