Targetable oncogenic pathways in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma

Classical Hodgkin lymphoma is a lymphoid neoplasm consisting of mononuclear Hodgkin and multinuclear Reed-Sternberg cells, mostly of B-cell origin, embedded in a non-neoplastic background. Most patients are cured with current risk- and response adapted therapy, albeit a portion of patients will either fail to respond or will relapse. An important drawback considering healed individuals is the increasing late toxicity, particularly the high incidence of secondary malignancies. Landmark discoveries from the recent decade point towards the significance of a few molecular pathways in classical Hodgkin lymphoma pathogenesis, to which Hodgkin and Reed-Sternberg cells are oncogenically addicted. Several players of these oncogenic pathways can be or are now targeted in in vitro and in vivo models as well as in early clinical trials. Some of these oncogenic pathways in Hodgkin and Reed-Sternberg cells that could form the basis for rational molecular modulations as well as current data from targeted-therapy studies aiming at these pathways will be summarized in the review.