Targeted molecular therapy in peripheral T-cell lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) are rare neoplasms constituting a heterogeneous group of diseases. At present, available chemotherapy regimens that have improved outcomes in B-cell lymphomas appear to be less efficacious in the context of PTCLs and, thus, alternative strategies are warranted. In the last few years, based on the recent, deeper understanding of PTCL biology, several molecules and/or pathways have been proposed for targeted therapy in this setting, including surface antigens, tyrosine kinases, the NF-κB pathway, folate metabolism, histone modification and others. Of particular interest, histone deacetylase and proteasome inhibitors, as well as novel chemotherapeutic agents such as pralatrexate, have already demonstrated efficacy in PTCL therapy. In addition, a strong biological rationale and early clinical evidence supports the future study of tyrosine kinase inhibitors in this setting. In this article, the authors review the available literature on targeted therapy in PTCLs and also, based on their own experience, discuss potential opportunities in this intriguing area.

Keywords::

• histone deacetylase inhibitors
• monoclonal antibodies
• peripheral T-cell lymphoma
• proteasome inhibitors
• targeted therapy
• tyrosine kinase inhibitors

Acknowledgements

The European T-cell Lymphoma Study Group: P Gaulard, AM Piris, L De Leval, G Inghirami, G Delsol, C Peeters, A Rosenwald, PP Piccaluga, SA Pileri, R Chiarle, R Piva, D Novero, M Chilosi, A Zamo, F Facchetti, S Ascani, M Ponzoni, F Bretoni, L Agnelli, A Neri, C De Wolf-Peeters, E Geissinger, HK Muller-Hermelink and C Tripodo. The authors are grateful to Marco Bettuzzi for figure editing.

Financial & competing interests disclosure

This work was supported by Centro Interdipartimentale per la Ricerca sul Cancro ‘G Prodi’, BolognAIL, AIRC (IG4987, IG10007 and 5xMille), RFO (to Stefano A Pileri and Pier Paolo Piccaluga), Fondazione Cassa di Risparmio in Bologna, Fondazione della Banca del Monte e Ravenna and Progetto Strategico di Ateneo 2006 (to Stefano A Pileri and Pier Paolo Piccaluga). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.