Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis - a review of current evidence

Expert Opin Ther Targets. 2023 Jul-Dec;27(11):1097-1113. doi: 10.1080/14728222.2023.2285784. Epub 2023 Dec 7.

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others.

Area covered: In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports.

Expert opinion: CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.

Keywords: Cyclin-dependent kinases; cyclin-dependent kinase inhibitors; inflammatory diseases; psoriasis; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid* / drug therapy
  • Cyclin-Dependent Kinases / pharmacology
  • Cyclin-Dependent Kinases / therapeutic use
  • Cyclins / pharmacology
  • Cyclins / therapeutic use
  • Cytokines
  • Fibroblasts
  • Humans
  • Psoriasis* / drug therapy

Substances

  • Cyclin-Dependent Kinases
  • Cytokines
  • Cyclins