Aggressive Lymphomas

Given the emergence of many new therapeutic agents that affect essential regulatory pathways in lymphomas, the challenge is to identify rational combinations that kill lymphoma cells synergistically. This effort requires both preclinical evaluation and the development of clinical-trial strategies that include molecular profiling. Gene-expression profiling could be used to determine the lymphoma subtype and to estimate the risk associated with standard therapy. Cancer-gene resequencing could be used to identify tumors that are likely to be dependent on a particular signaling pathway and to determine which step in the pathway to inhibit. Finally, the activity of the targeted pathways before and during therapy could be used to assess the efficacy of the treatment. We expect that this “divide-and-conquer” approach will provide increasingly effective and nontoxic therapies for patients with lymphoma.