Interplay between proteasome inhibitors and NF-κB pathway in leukemia and lymphoma: a comprehensive review on challenges ahead of proteasome inhibitors

Cell Commun Signal. 2024 Feb 8;22(1):105. doi: 10.1186/s12964-023-01433-5.

Abstract

The current scientific literature has extensively explored the potential role of proteasome inhibitors (PIs) in the NF-κB pathway of leukemia and lymphoma. The ubiquitin-proteasome system (UPS) is a critical component in regulating protein degradation in eukaryotic cells. PIs, such as BTZ, are used to target the 26S proteasome in hematologic malignancies, resulting in the prevention of the degradation of tumor suppressor proteins, the activation of intrinsic mitochondrial-dependent cell death, and the inhibition of the NF-κB signaling pathway. NF-κB is a transcription factor that plays a critical role in the regulation of apoptosis, cell proliferation, differentiation, inflammation, angiogenesis, and tumor migration. Despite the successful use of PIs in various hematologic malignancies, there are limitations such as resistant to these inhibitors. Some reports suggest that PIs can induce NF-κB activation, which increases the survival of malignant cells. This article discusses the various aspects of PIs' effects on the NF-κB pathway and their limitations. Video Abstract.

Keywords: Lymphoma; NF-κB, leukemia; Proteasome; Proteasome inhibitors.

Publication types

  • Video-Audio Media
  • Review

MeSH terms

  • Apoptosis
  • Hematologic Neoplasms*
  • Humans
  • Leukemia* / drug therapy
  • Lymphoma* / drug therapy
  • NF-kappa B / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use

Substances

  • Proteasome Inhibitors
  • NF-kappa B
  • Proteasome Endopeptidase Complex