Dr. Bhalla on Sensitizing TNBC to PARP Inhibitors and Cisplatin

Kapil N. Bhalla, MD, chief of personalized cancer medicine at the University of Kansas Cancer Center in Kansas City, describes the findings from an in vitro study that examined treatment with histone deacetylase (HDAC) inhibitors in triple-negative breast cancer (TNBC) cells.

Treatment with pan-HDAC inhibitors such as vorinostat and panobinostat can induce Hsp90 hyperacetylation, which causes depletion in BRCA levels and other DNA response proteins. This treatment produces a DNA repair deficit within the TNBC cells while also causing DNA damage. This results in a treatment scenario that mimics what is observed with BRCA mutations.

Bhalla adds that inducing BRCAness from treatment with a HDAC inhibitor allows for effective combination strategies with PARP inhibitors or cisplatin. These combinations could result in a synergistic treatment approach in TNBC.

This study provides the rationale to test cisplatin, HDAC, and PARP inhibitor combination strategies in patients with TNBC with or without the presence of a BRCA1/2 mutation.

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