Why ACE—overview of the development of the subtype-selective histone deacetylase inhibitor chidamide in hormone receptor positive advanced breast cancer

ACE stands for “A Phase III Trial of Chidamide in Combination with Exemestane in Patients with Hormone Receptor-Positive Advanced Breast Cancer”. Chidamide, or by its International Nonproprietary Name (INN), tucidinostat, is an oral subtype-selective histone deacetylase (HDAC) inhibitor with unique epigenetic modulating mechanisms for anti-cancer treatment. Chidamide has been approved in China for the indications of relapsed or refractory peripheral T-cell lymphoma, and hormone receptor-positive (HR+) advanced breast cancer. In the current review, epigenetic regulations and HDACs, the potential roles of epigenetic aberrations in disease progression and resistance to endocrine therapy in HR+ breast cancer, and the development of HDAC inhibitors as a promising therapeutic strategy in the field are overlooked. Then the review focuses on the ACE study in its rationale, trial design and results that led to the first-in-disease approval of chidamide in the epigenetic modulating drug class in breast cancer.