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INTRODUCTION: most patients with classical Hodgkin's lymphoma (cHL) are cured by stage-adapted multimodal regimens. However, some will suffer from refractory disease or experience a relapse. Furthermore, late toxicity due to aggressive chemotherapy and/or radiotherapy has become an increasing problem in long-term survivors. Special situations, such as cHL in a post-transplant setting and patients not able to tolerate standard therapy, are also challenging. Targeting molecular pathways could be a way to find solutions for these varied aspects. AREAS COVERED: research undertaken by leading experts in the field of cHL is summarized. The literature search encompasses all data available via PubMed or published (pre-)clinical trials until August 2010. We discuss the crucial molecular pathways in cHL, novel agents that may be utilized to interact with these pathways, and insights into the results of current clinical trials utilizing these novel therapeutics. EXPERT OPINION: the most important oncogenic pathways in cHL are loss of B-cell identity by the neoplastic cells, activation of the NF-?B pathway, and constitutive activation of the JAK2-STAT-pathway. Both monoclonal antibodies and small-molecule inhibitors are potentially useful agents to target these pathways.
