Adjusting Speed of Cancer Cell DNA Repair Vital to Overcome Chemotherapy Resistance

By wrapping around cancer cell DNA and forming a protective shield, histones help speed up the repair process and increase chemotherapy resistance, according to a study published in Nucleic Acids Research.

A majority of chemotherapies and radiotherapies kill cancer cells by creating breaks in the DNA, but cancer cells are able to resist treatment by fixing the breaks.

“If we can find a way to hijack the cancer’s fix and repair toolkit and make it less efficient, then we can tip the scale in favor of cancer cell death instead of survival and prevent resistance to chemotherapy,” said lead researcher Sherif El-Khamisy.

Findings from a new study indicate that the key to preventing treatment resistance to a common class of chemotherapy used on breast and colon cancer patients is to change the speed that cancer cells repair the damage to their DNA.

“We have discovered that resistance to a common class of chemotherapy, used to treat colon and breast cancer, is caused by changes in the speed by which the tool kit components travel to, and stay at, the sites of DNA breaks,” El-Khamisy said. “Our researchers were able to identify a change in a specific mark in the proteins that wrap the DNA — called histones – in such a way that makes repair much faster in cancer cells, increasing their resistance to therapy. The change we identified is not genetic – but epigenetic.”

The findings indicate that patients who develop treatment resistance to certain classes of chemotherapy can benefit from drugs that modulate histone marks, such as histone deacetylase inhibitors.

“We only focused on a class of chemotherapy used to treat colon and breast cancer called topoisomerase 1 inhibitors,” El-Khamisy said. “It is possible that the same mechanism holds true for other classes of chemotherapy.”