HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women

• Main Authors: Sara S. Oltra, Juan Miguel Cejalvo, Eduardo Tormo, Marta Albanell, Ana Ferrer, Marta Nacher, Begoña Bermejo, Cristina Hernando, Isabel Chirivella, Elisa Alonso, Octavio Burgués, Maria Peña-Chilet, Pilar Eroles, Ana Lluch, Gloria Ribas, María Teresa Martinez
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Cancers
• Subjects: breast cancer; young women; histone deacetylase; hdac5 inhibitors; lmk-235
• Online Access: https://www.mdpi.com/2072-6694/12/2/412

Background: Breast cancer in very young women (BCVY) defined as &lt;35 years old, presents with different molecular biology than in older patients. High <i>HDAC5</i> expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze <i>HDAC5</i> expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: <i>HDAC5</i> expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher <i>HDAC5</i> expression with worse prognosis in BCVY. However, we observed no differences between <i>HDAC5</i> expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of <i>HDAC5</i>. Overexpression of <i>HDAC5</i> in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.