Biologic Basis of Novel Therapeutic Strategies in Hodgkin Lymphoma

Haema 2012; 3(3): 250-259

by Elias Drakos¹, George Rassidakis²

¹Lecturer of Pathology, Medical School, University of Crete, Greece,
²Assistant Professor of Pathology, School of Medicine, National and Kapodistrian University of Athens, Greece, Adjunct Assistant Professor of Hematopathology The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

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Abstract

The development of traditional treatment for Hodgkin lymphoma patients remains one of the most successful efforts in cancer therapeutics. Surprisingly, this success was largely accomplished independently of the understanding of the disease biology. However, even today a proportion of patients succumb to the disease and the long term treatment side effects remain considerably debilitating. Nowadays, accumulating biological knowledge gained from recent studies that explored the mechanisms of Hodgkin lymphoma pathogenesis provides a solid basis and rationale for the development of novel experimental, and biologically more targeted, therapeutic approaches. Among others, understanding of the significance of activation of NF-kB transcription factor and the PI3K-AKT-mTOR signaling pathway, as well as the potential role the CD30 receptor for the survival and proliferation of Hodgkin and Reed- Sternberg neoplastic cells has revealed new therapeutic molecular targets for the disease. In addition, modulation of the p53 tumor suppressor pathway using non-toxic small molecules may provide a promising targeted therapeutic strategy in near future. Based on the biology of disease, selection of patients in newly designed clinical trials should take into account both genetic (i.e. gene mutations) and signaling pathway markers to better define subgroups for personalized therapeutic interventions. Application of novel therapeutic agents based on specific molecular targets has already been translated in a multitude of clinical trials providing encouraging results in an effort to increase the curative potential and de- crease the therapeutic side effects patients with Hodgkin lymphoma.