Some lymphomas become resistant to treatment. Gene discovery may offer path to overcome it.

University of Wisconsin–Madison researchers have uncovered a critical process driving resistance in certain types of lymphoma, offering hope for patients who become resistant to standard treatments. The study focused on understanding why some patients with B-cell malignancies, such as mantle cell lymphoma and diffuse large B-cell lymphoma, develop resistance to Bruton tyrosine kinase inhibitors (BTK inhibitors) like ibrutinib.

While BTK inhibitors initially show promise in treating these cancers by blocking abnormal B-cell production, many patients relapse after one or two years of treatment, posing a significant challenge. The researchers identified a key gene, EGR1, responsible for producing a protein that promotes resistance to ibrutinib. They found that resistant malignant B cells had increased activity of EGR1, leading to enhanced energy production and drug resistance.

To combat this resistance, the team tested a novel treatment approach using two drugs, metformin and IM156, to target the overactivity of EGR1. In mouse models with drug-resistant B-cell lymphomas, this combination therapy effectively slowed cancer cell growth. The researchers aim to translate these findings into clinical trials, offering new hope for lymphoma patients facing relapse due to drug resistance.