Preclinical strategies to identify novel drug combinations often prioritize synergistic drug combinations: those which perform better than would be expected based on the monotherapy activities. In this issue, Mason-Osann et al. use live cell imaging to demonstrate that synergistic drug combinations increase the likelihood of resistance developing and the fitness benefit conferred by resistance, because resisting one drug disrupts the synergy. This experimental data is supported by computational modeling, and analysis of patient-derived tumor xenografts and clinical data. These findings suggest a reevaluation of preclinical screening, emphasizing response durability and cautioning against prioritizing combinations of individually weak drugs based on short-term synergy.

See article, p. 95.

Clinical responses to CD19-targeting CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (rrLBCL), while encouraging, remain heterogeneous and are often accompanied by serious immunotoxicities. In this work, Faramand, Lee, Jain et al. offer a simple risk stratification system identifying risks of high-grade immune-related...

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