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

HDAC5 抑制剂有望成为治疗年轻女性乳腺癌的潜在药物

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作者: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

Background

Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines.

Conclusions

In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.

Methods

HDAC5 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 HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 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 HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.

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