KDM4 inhibition targets breast cancer stem-like cells

Authors: Metzger, E., et al.

Source: Cancer Research doi: 10.1158/0008-5472.CAN-17-1754

cancerres.aacrjournals.org/content/early/2017/09/07/0008-5472.CAN-17-1754

Currently, TNBC has the worst prognosis among cases of breast cancer. One reason for this is that less is known about this type of breast cancer compared to other breast cancers. Therapies that specifically target TNBC do not exist.

The researchers investigated the KDM4 family of enzymes. These substances are known to control cell reproduction — particularly, the reproduction of more aggressive breast cancer cells. They sought to test the effectiveness of a KDM4 inhibitor, called QC6352, as a way to slow down or stop TNBC cell growth.

A line of TNBC cells was needed for the study, and the investigators were aware that finding a consistent line of breast cancer stem cells (cells of origin) is difficult. The conditions to maintain such cells are often ineffective. So, they created an environment to support the continuous growth of breast cancer stem cells from human breast cancer tumors.

Using their cultivated TNBC cells, the group then confirmed that these cells used KDM4 for reproduction. This allowed them to use KDM4 enzymes as targets to stop TNBC cell growth. QC6352 is an oral agent that inhibits the action of KDM4. When it was applied to the TNBC cells, these cells were then blocked from reproducing.

The team’s results have two benefits: providing a new model for creating breast cancer cell lines and calling attention to a potential TNBC target for effective therapy.