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Integration of the proteasome inhibitor PS-341 (Velcade) into the therapeutic approach to lung cancer

2003; Elsevier BV; Volume: 41; Linguagem: Inglês

10.1016/s0169-5002(03)00149-1

1872-8332

Philip C. Mack, Angela M. Davies, Primo N. Lara, Paul H. Gumerlock, David R. Gandara,

Cancer Mechanisms and Therapy

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, p27Kip1, p53, NF-κB, 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.