Related Experiment Video
Updated: Mar 9, 2026
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
HDAC10 as a potential therapeutic target in ovarian cancer
Muhtadi M Islam1, Tapahsama Banerjee1, Colin Z Packard1
1Department of Biomedical Informatics, The Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, United States.
Objective:
We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy.
Methods:
We combined informatics analysis of large DNA sequencing datasets from ovarian cancer tumors with tissue culture based assays of primary and established cell lines to test for sensitivity to platinum therapy if HDAC10 activity was inhibited or depleted.
Results:
Using The Cancer Genome Atlas (TCGA) dataset, we found that deep deletions in HDAC10 occurred in 5-10% of ovarian cancer tumors. From the TCGA data we found that low HDAC10 mRNA levels correlated with platinum sensitivity of the tumors. Cell proliferation and DNA damage assays in a BRCA1-null ovarian carcinoma cell line demonstrated reduced DNA repair capacity and sensitization of platinum therapy. Similarly, primary ovarian carcinoma cells demonstrated a sensitization to platinum therapies when treated with HDAC inhibitors.
Conclusions:
From the results of this study, we suggest that the inhibition of HDAC10 may potentiate the effects of platinum therapies in ovarian tumors.
Insights
Inhibiting histone deacetylase 10 (HDAC10) may enhance platinum therapy effectiveness in ovarian cancer. Reduced HDAC10 levels correlate with better platinum sensitivity in tumors, sensitizing cells to treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Histone deacetylase 10 (HDAC10) plays a role in DNA repair pathways.
- Ovarian cancer treatment often involves platinum-based chemotherapy.
- Understanding DNA damage response in BRCA1-null cells is crucial for targeted therapies.
Purpose of the Study:
- To investigate the role of HDAC10 in the DNA damage response of BRCA1-null ovarian cancer cells.
- To evaluate the potential of HDAC inhibitors in primary ovarian carcinoma cells.
- To determine if inhibiting HDAC10 sensitizes ovarian cancer cells to platinum therapy.
Main Methods:
- Analysis of The Cancer Genome Atlas (TCGA) dataset for HDAC10 alterations in ovarian tumors.
- In vitro assays using BRCA1-null ovarian carcinoma cell lines to assess DNA repair and platinum sensitivity.
- Treatment of primary ovarian carcinoma cells with HDAC inhibitors to evaluate platinum therapy response.
Main Results:
- Deep deletions in HDAC10 were found in 5-10% of ovarian tumors.
- Low HDAC10 mRNA levels correlated with platinum sensitivity.
- HDAC10 inhibition or depletion reduced DNA repair capacity and sensitized BRCA1-null cells and primary ovarian cells to platinum therapy.
Conclusions:
- HDAC10 inhibition shows potential to potentiate platinum therapies in ovarian tumors.
- Targeting HDAC10 could be a strategy to improve ovarian cancer treatment outcomes.
- Further research into HDAC inhibitors for ovarian cancer is warranted.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:56Treatment Resistant Cancers
01:30Hormonal Control of the Ovarian Cycle
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...