New targets for lymphoma treatment

Abstract

The rapid development in understanding the biology oflymphoid cells has led to the identification of multiplepathways and targets for therapy in recent years. These rangefrom cell surface interactions involving the B-cell receptor(BCR), through signalling pathways such as that mediated viathe mammalian target of rapamycin (mTOR) and NF-jB,modulation of gene expression by histone acetylation, controlof protein degradation by the proteosome or heat shockproteins, and regulation of apoptosis by both surface deathreceptors and intracellular proteins. In addition, a variety ofstrategies for driving immune responses to lymphoma havebeen investigated, including the use of small moleculeimmunomodulators, and agonistic antibodies which targetimmune cells rather than the malignant cells themselves.Finally, the idiotype remains an attractive target for B-celllymphoma, being wholly patient specific, and vaccinationstrategies aimed at raising humoral and cellular responses are atan advanced stage of clinical study. The development of allthese agents remains at an experimental stage, with none havingas yet delivered clear advantages in terms of overall survival inphase III trials, although some are getting close. In many casesnovel combinations are in clinical testing, with eitherconventional cytotoxics, monoclonal antibodies or several newagents together. A deeper understanding of their mechanismsof action should allow the rational development of suchcombinations in the near future.