Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia

Expert Rev Mol Med. 2023 May 3:25:e16. doi: 10.1017/erm.2023.13.

Abstract

This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia-niche interactions. The tumour microenvironment plays an integral role in conferring treatment resistance to leukaemia cells, this poses as a key clinical challenge that hinders management of this disease. Here we focus on the role of the cell adhesion molecule N-cadherin (CDH2) within the malignant BM microenvironment and associated signalling pathways that may bear promise as therapeutic targets. Additionally, we discuss microenvironment-driven treatment resistance and relapse, and elaborate the role of CDH2-mediated cancer cell protection from chemotherapy. Finally, we review emerging therapeutic approaches that directly target CDH2-mediated adhesive interactions between the BM cells and leukaemia cells.

Keywords: Anti-cancer drugs; CDH2; cancer microenvironment; leukaemia; treatment resistance.

Publication types

  • Review

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, CD / therapeutic use
  • Bone Marrow* / metabolism
  • Bone Marrow* / pathology
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cadherins / therapeutic use
  • Cell Adhesion
  • Child
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Tumor Microenvironment

Substances

  • Cadherins
  • CDH2 protein, human
  • Antigens, CD