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

Lung Cancer. 2003 Aug;41 Suppl 1:S89-96. doi: 10.1016/s0169-5002(03)00149-1.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Boronic Acids / administration & dosage*
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Cell Cycle
  • Clinical Trials as Topic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Protease Inhibitors / administration & dosage*
  • Protease Inhibitors / pharmacology*
  • Pyrazines / administration & dosage*
  • Pyrazines / pharmacology*
  • Ubiquitin / physiology

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Ubiquitin
  • Bortezomib