This article reviews the most recent developments and implications in regard to isocitrate dehydrogenase mutations in chondrosarcoma, a disease in which currently available systemic therapies have proven inefficacious, with an emphasis on how disruption in normal cellular metabolism plays a role in oncogenesis.
The development of acquired isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutations has been described in multiple tumors and more recently in chondrosarcomas. The impact of these mutations has been the focus of multiple research efforts during the last years, allowing us to better understand the impact of the mutation, including its interaction with other proteins, changes in expression of genes involved in tumor genesis, the oncogenic potential of 2-hydroxyglutarate, the impact on cellular proliferation and differentiation, and the influence on the epigenetic state of cells owing to changes in DNA and histone methylation patterns. New compounds targeting the mutation have been developed.
This mutation is the first of its kind described in chondrosarcoma, serving as an identifying marker of chondroid differentiation, and becoming the first molecular target with potential anticancer effect, translating into the development of therapies targeting these mutations currently being tested further in preclinical models and clinical trials.
aDivision of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
bEscolaBahiana de Medicina e SaudePublica, Brotas, Salvador, BA, Brazil
Correspondence to Michel Velez, MD, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, D8–4, Miami, FL 33136, USA. Tel: +1 305 243 6554; fax: +1 305 243 3289; e-mail: firstname.lastname@example.org