The activity of HDAC and mTOR inhibitors in three dimensional in-vitro model of BRCA-2 mutated breast cancer cell line.

e22221 Background: Targeted therapies for breast cancer patients carrying BRCA-1/2 mutations are emerging. Histone deacytelase inhibitors (HDACi) represent a promising class of drugs for the treatment of breast cancer. Previous studies had shown that HDACi down regulate multiple components of DNA damage response and repair. There is also an evidence that PI3K/mTOR inhibition potentiates HDAC inhibition activity in some tumors. Therefore, we explored the efficacy of HDACi and mammalian target of rapamycin inhibitor (mTORi) and their combination in BRCA-2 mutated breast cancer cell line. Methods: The activity of HDACi (scriptaid) and mTORi (everolimus) as single agent or in combination was evaluated in 3 breast cancer cell lines (MCF-7, ER+; MDA-MB-231, ER-; BCSV, cell line derived from BRCA-2 mutated metastatic breast cancer which was ER positive and Her-2 negative at diagnosis but lost ER expression during tumor progression). The effects of the treatment were determined by a colorimetric MTT assay, Ki67 e...