Beyond monoclonal antibodies: new therapeutic agents in non-Hodgkin's lymphomas.
The availability of active monoclonal antibodies, either as single agents or in combination with cytotoxic agents, has improved treatment results in non-Hodgkin's lymphoma (NHL). Despite this and the increasing number of available active monoclonal antibodies, alone or conjugated with radioisotopes, not all types of lymphoma are sensitive to these biological agents and often they become resistant because of different molecular mechanisms. New molecular targets in neoplastic cells are emerging and provide the rationale for novel discovery initiatives. In fact, a greater knowledge of the biology of lymphoma and the identification of compounds selectively active against a potential therapeutic pathway have already improved the time to progression and survival time of patients with some subtypes of NHL. The growing list of new drugs provides the exciting prospect of developing disease-specific and even patient-specific therapies. The aim of this review is to identify and discuss non-monoclonal antibody new therapeutic agents in terms of mechanism of action and clinical results. The preclinical and clinical features of proteasome inhibitors, histone deacetylase inhibitors, thalidomide and lenalidomide, mammalian target of rapamycin inhibitors, antisense oligonucleotides, heat shock protein inhibitors, protein kinase C inhibitors, antiangiogenic agents, and new cytotoxics are reviewed.
Oncology Institute of Southern Switzerland, Ospedale S. Giovanni, 6500 Bellinzona, Switzerland. angelo.delmonte@eoc.ch
Angelo
A
Delmonte
Michele
M
Ghielmini
Cristiana
C
Sessa
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011719:Pyrazines / Q000627:therapeutic use; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D001897:Boronic Acids; D018841:HSP90 Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D016376:Oligonucleotides, Antisense; D061988:Proteasome Inhibitors; D011719:Pyrazines; C401859:temsirolimus; D000069286:Bortezomib; D011493:Protein Kinase C; D020123:Sirolimus