Proteasome inhibition with PS-341 (bortezomib) in lung cancer therapy.
PS-341 (bortezomib) represents a new class of therapeutics that targets the ubiquitin-proteasome pathway. It has broad-spectrum single-agent anticancer activity and can potentiate chemotherapy and radiation in preclinical models. Early phase clinical studies have shown tolerability and activity in multiple myeloma, lymphoma, prostate cancer, and lung cancers. By its mechanism of inhibiting protein degradation, PS-341 targets a wide range of pathways relevant to tumor progression and therapy resistance and can directly modulate expression of cyclins, p27(Kip1), p53, nuclear factor-kappaB, Bcl-2, and Bax. PS-341 is currently in phase I/II clinical development in both non-small cell lung cancer and small cell lung cancer. This article will review the preclinical and clinical experience with PS-341 as it relates to lung cancer.
Lara
Primo N
PN
Department of Internal Medicine, University of California Davis School of Medicine, UCD Cancer Center, Sacramento 95817, USA.
Davies
Angela M
AM
Mack
Philip C
PC
Mortenson
Melinda M
MM
Bold
Richard J
RJ
Gumerlock
Paul H
PH
Gandara
David R
DR
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease