Integration of the proteasome inhibitor PS-341 (Velcade) into the therapeutic approach to lung cancer.
PS-341, a potent and selective proteasome inhibitor, is the prototype for a new class of therapeutics that targets the ubiquitin-proteasome pathway. It is active as a single agent and potentiates chemotherapy and radiation in pre-clinical models. Early phase clinical studies have demonstrated tolerability and activity in multiple myeloma, lymphoma, prostate cancer and lung cancer. By its mechanism of inhibiting protein degradation, PS-341 targets a wide-range of pathways that are relevant to tumor progression and therapy resistance, and can directly modulate expression of cyclins, p27(Kip1), p53, NF-kappaB, Bcl-2 and Bax. PS-341 is currently in phase I/II clinical development in lung cancer. This paper will review the pre-clinical and clinical experience with PS-341 as it relates to lung cancer.
Mack
Philip C
PC
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Sacramento, CA 95817, USA. pcmack@ucdavis.edu
Davies
Angela M
AM
Lara
Primo N
PN
Gumerlock
Paul H
PH
Gandara
David R
DR
D001897:Boronic Acids / Q000008:administration & dosage* / Q000494:pharmacology*; D000069286:Bortezomib; D002453:Cell Cycle; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology*; D025801:Ubiquitin / Q000502:physiology
D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib