Cancer cells have a bias toward survival, often becoming heavily reliant on certain protein pathways to sustain themselves. Scientists are finding ways to turn that survival instinct into a liability — by making the cells even more dependent on those pathways, then choking the pathways off. It’s an approach that has now yielded a promising combination drug therapy for T-cell prolymphocytic leukemia (T-PLL), a rare, aggressive hematologic cancer. In a recent study in the journal Blood, Dana-Farber researchers analyzed blood samples from two dozen patients with T-PLL and found that pairing the targeted drugs ruxolitinib and venetoclax caused T-PLL cells to die in the laboratory. When they tested the combination in two patients with advanced T-PLL, the results were encouraging: one patient experienced a deep remission, and the other, whose cancer was rapidly worsening, saw the advance of the disease come to halt. “T-PLL is an especially challenging cancer to treat. The current treatments, such as chemotherapy and the antibody drug alemtuzumab, aren’t very effective and lead to considerable toxicities,” says Dana-Farber’s Matthew Davids, MD, senior author of the study. “We urgently need to identify the molecular vulnerabilities of T-PLL cells so we can design clinical trials of drugs that target those weaknesses. Our study is one of the first to do that.”
