A protein that can dial down oxidative stress in cells helps some cancers resist treatment with a widely used class of drugs called BTK inhibitors, according to a study led by investigators at Weill Cornell Medicine. The discovery points to a possible solution to the problem of BTK inhibitor treatment resistance.
BTK inhibitors reduce the activity of the enzyme BTK (Bruton’s Tyrosine Kinase), which has a central role in immune cells called B cells. Inhibiting BTK chokes off the ability of B cells to proliferate, which has benefits against some blood cancers including several types of lymphoma. Unfortunately, these malignancies often lose their sensitivity to BTK inhibitors after a year or two of treatment. In the study, published July 2 in Nature Communications, the researchers discovered that in mantle cell lymphoma, a common mechanism of resistance to BTK inhibitors involves aberrant activity of a protein called BRG1. They found that BRG1 protects cells from BTK-inhibitor treatment by suppressing a cell-killing process called ferroptosis, an iron-dependent form of cell death that BTK inhibitors otherwise induce.
