Ovarian cancer often grows undetected into the advanced disease stages and because of this the mortality rate is relatively high. Even after using the available treatments, relapse is quite common. Recent studies of several cancers have shown positive impacts when treated with HDAC inhibitors, and even more powerful impacts when treated with an HDAC inhibitor paired with other types of inhibitors.
A recent study on ovarian cancer cells paired HDAC inhibitor panobinostat (LBH-589) with autophagy inhibitor chloroquine or bafilomycin A1. Together they cause DNA strand breaks and inhibit the cell’s ability to repair those breaks. The combination treatment was more powerful than the individual treatments. Discovering synergistic drug combinations such as these is the cornerstone of cancer therapy.
In another study, panobinostat was paired with PARP inhibitor olaparib. Mice with epithelial ovarian cancer cells were divided into 4 groups and each group subjected to one set of treatment: vehicle, panobinostat, olaparib, or panobinostat + olaparib. It was discovered that PARP inhibitors and HDAC inhibitors synergize well against HR-proficient ovarian cancer. This is exciting because HR-proficient type has proven less responsive to the developed treatments than HR-deficient type, which is more common. The overall tumor burden in the mice treated with panobinostat + olaparib was reduced. Also, there was reduced tumor proliferation and increased DNA damage observed in the harvested tumors.
Using the dual mechanisms of an HDAC inhibitor combined with another type of inhibitor is found to have a synergistic effect in many instances. The rational combination of drugs to target both cytotoxic effects and immune-modulating effects at the same time increases the potential to overcome drug resistance. This is especially important in fighting cancers such as ovarian cancer that have high mortality rates.
Ovejero-Sanchez M, Gonzalez-Sarmiento R, Herrero AB. Synergistic effect of chloroquine and panobinostat in ovarian cancer through induction of DNA damage and inhibition of DNA repair. Neoplasia. 2021 May;23(5):515-528. doi: 10.1016/j.neo.2021.04.003. PMID: 33930758
Wilson A, Gupta V, Liu Q, et al. Panobinostat enhances olaparib efficacy by modifying expression of homologous recombination repair and immune transcripts in ovarian cancer. Neoplasia. 2022 Feb;24(2):63-75. doi: 10.1016/j.neo.2021.12.002. PMID: 34933276