Proteasome Inhibitors In Cancer Therapy: A Novel Approach To A Ubiquitous Problem

Kristin R. Landis-Piwowar

doi:10.29074/ascls.25.1.38

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Kristin R. Landis-Piwowar, PhD,MT(ASCP)⇑
1. Oakland University, School of Health Sciences, Biomedical Diagnostic and Therapeutic Sciences, Rochester, MI

Address for Correspondence: Kristin Landis-Piwowar, Ph.D. MT (ASCP), School of Health Sciences, 321 HHS, Oakland University, 2200 N. Squirrel Rd, Rochester, MI 48309, 248-370-4039, landispi{at}oakland.edu

Describe the basic structure and function of the proteasome.
Identify the proteasomal subunit within the catalytic core that is crucial to cell survival.
List proteasome protein targets.
Evaluate the effect on cellular homeostasis following proteasome inhibition.
Detail the status of various proteasome inhibitors in pre-clinical and clinical trials.

Abstract

The cellular proteasome is an important molecular target in cancer therapy and drug resistance research. Proteasome inhibitors are effective agents against multiple myeloma and mantle cell lymphoma and display great potential as treatment for a variety of other malignancies. The proteasome is a large multicatalytic, proteinase complex located in the cytosol and the nucleus of eukaryotic cells. The ubiquitin proteasome system is responsible for the degradation of most intracellular proteins and therefore plays an essential regulatory role in critical cellular processes including cell cycle progression, proliferation, differentiation, angiogenesis, and apoptosis. Cancer cells are particularly sensitive to proteasome inhibitors, indicating the utility for inhibition of the ubiquitin-proteasome pathway as an approach for cancer therapy.