Genetic Signatures Could Predict Treatment Resistance for Ovarian Cancer

The drug HXR9 was shown to block HOX expression in ovarian cancer cells.

A recently discovered gene signature could predict survival for patients with ovarian cancer. These genetic signatures could potentially identify patients who may become treatment resistant.

Researchers analyzed HOX genes, and how they relate to ovarian cancer treatment resistance, according to a study published in the International Journal of Cancer. The HOX genes enable rapid cell division in embryos, but are typically switched off in adults except in patients with certain cancers.

Researchers examined tissue samples from 99 patients with epithelial ovarian cancer (EOC) compared with healthy tissues. They found that 36 of 39 HOX genes were seen in high levels of tissue samples in patients with EOC, which suggests the high grade serious subtype compared with little to no HOX expression in healthy ovarian tissue, according to the study.

A 5-gene signature was discovered in patients who died from the cancer. The researchers then tested HXR9, a peptide drug that blocks HOX expression on cancer cells and in mice.

"The results in mice were encouraging, but more muted: treated mice survived for longer, but the cell killing of the combination approach was only marginally better than HXR9 used on its own,” said co-author Zoe Kelly, PhD. “However, these tests were carried out over a very short timeframe, and I believe that more extensive tests in the mouse model would show clearer results. This needs to be the next step for this research."

They discovered a combination of HXR9 and cisplatin significantly increased cancer cell death compared with either drug alone.

"This is the first comprehensive analysis of HOX gene expression in ovarian cancer and the first study to analyze changes in HOX expression in resistant cancer cells,” lead researcher Richard Morgan, PhD concluded. “The results strongly suggest that targeting these genes as a new treatment approach warrants further investigation. It also supports our belief that HXR9 should be further developed and tested in clinical trials."