The immune system cancer known as lymphoma can often be cured, but some types remain stubbornly resistant to treatment. Now researchers have found a drug that appears to help vanquish these lymphomas by targeting their abnormal cell wiring. Tumors shrank in four of 10 advanced lymphoma patients treated with the drug, and one is still in remission more than a year later.
Diffuse large B-cell lymphoma, which involves immune cells called B cells, is one of the more common and dangerous lymphomas. Each year about 23,000 people in the United States are diagnosed with it, and some 10,000 die annually. Over the past decade, cancer biologist Louis Staudt’s team at the National Cancer Institute in Bethesda, Maryland, has analyzed patterns of gene activity within the malignant immune cells to break this cancer into subtypes, including one, activated B-cell-like (ABC) diffuse large B-cell lymphoma, that kills 60% of patients within 3 years. By dissecting the roles of different genes and proteins in the lymphoma cells, Staudt and colleagues have uncovered what appears to go wrong in this cancer: Genetic mutations cause B-cell receptors, proteins on the B cell’s surface that normally recognize infections, to send signals into the cell that block a self-destruction process that normally helps rid the body of abnormal cells. In lab studies, the lymphoma cells died when treated with an experimental drug called ibrutinib that overrides this anti-suicide signal. The drug blocks a protein called Bruton’s tyrosine kinase (BTK) that’s part of the B-cell-receptor signaling pathway.