As news of first Batman actor died of Leukemia disturbed many on Saturday, came another news cheering those suffering from blood cancer that a new drug has proved successful to treat the disease. Leukaemia is a disease where the body produces too many white blood cells and not enough red blood cells.
The new drug, developed by Srividya Bhaskara, an Indian-origin postdoctoral at the University of Utah, may provide better treatment either solo or combined with chemotherapy to Acute lymphoblastic leukaemia (ALL) that can affect both children and adults.
Also known as Philadelphia chromosome, where two segments of chromosomes have aberrantly fused together, the ALL cancer cells are addicted to repairing DNA, which means these “cells do not retain enough DNA damage to die (from chemotherapy). Essentially they resist any kind of drug you use on them. So we had to find a new way to overcome this DNA repair addiction,” she said.
Srividhya focused on two specific proteins which she found were directly involved in DNA repair, called histone deacetylases (HDAC) 1 and 2 and then collaborated with a company to make a drug that inhibits HDAC1 and 2 activity.
When she tested the HDAC1,2 inhibitor in patient samples and mice, she found encourging results, either alone or in combination with a chemotherapy drug called doxorubicin currently used for Philadelphia chromosome-positive ALL patients.
she found that the drugs broke down the central hub of DNA repair, and the HDAC1,2 inhibitor actually reduced different repair protein functions.”When the drug was combined with a low concentration of doxorubicin, it had additional therapeutic benefits,” she said.
In fact, the mice treated with the HDAC1,2 inhibitor or the HDAC1,2/doxorubicin combination, showed that their bone marrow started turning from pale to red, indicating the white blood cells were being replaced with red blood cells.
“We completely nailed down how the HDAC1,2 inhibitor affects DNA repair. This is so important, not just for this cancer, but any cancer that is repair-addicted. We know there is a specific type of lymphoma that is also repair-addicted,” said Srividhya.
The study was published in the journal Leukemia.
In addition, the repair proteins identified by her can also be used as potential biomarkers to predict a patient’s response in the clinic. The next steps will include initiating human clinical trials, which are now being discussed between her team and appropriate clinical and pharmaceutical partners.