Triple negative breast cancer is one of the most aggressive, with the worst prognosis and without targeted therapy, although ignorance about it prevents knowing how to curb resistance to treatments such as chemotherapy. Now a group of experts has discovered something else about this mechanism.
Specifically, a new work led by Sandra Peiró, principal investigator of the Chromatin Dynamics Group in Cancer of the Vall d'Hebron Institute of Oncology (VHIO), has discovered that the DNA of tumor cells of this type of cancer is very much more compacted than usual compared to other types of tumor cells, which causes greater resistance to chemotherapy. As Peiró explains, “this makes it more difficult for drugs based on DNA damage to have access to this DNA, thus producing resistance to this type of treatment”, in this type of triple negative cancer.
This work has been published in the magazine Oncogene, and points out how chromatin decompaction could help improve the efficacy of these drugs in triple negative breast cancer. To reach this conclusion, the research team has been able to verify how the oxidation of histone H3 is key in the induction of DNA compaction and how this compaction would be related to treatment resistance.
A LOXL2 inhibitor
On the other hand, this same work has allowed us to observe that the inhibition of the LOXL2 enzyme would prevent this compaction from occurring, which has been seen to be very common in triple negative breast cancer, and that hindered the access of drugs to nucleus of tumor cells. “This occurs in different types of tumors, but we have seen that in those with triple negative breast, which are the most resistant to conventional drugs, this LOXL2 enzyme occurs in a large amount. This could indicate that it is one of the resistance mechanisms of these tumors, ”Peiro said.
Thus, although at the moment it has only been possible to test in cells in vitro and in mouse models, the data obtained indicate that an inhibition of LOXL2 in combination with conventional chemotherapy drugs could have relevant results in the treatment of triple breast cancer negative.