Mechanisms of action of tasquinimod on the tumour microenvironment

E. Raymond, A. Dalgleish, J. E. Damber, M. Smith, Roberto Pili

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

Tasquinimod is a small molecule with pleiotropic effects on the tumour microenvironment. Tasquinimod inhibits the growth and metastasis of tumour cells in vitro and in vivo. It targets the tumour microenvironment, enhancing the host immune response and inhibiting the angiogenic response. Tasquinimod influences infiltrating myeloid cells in the tumour milieu shifting the balance towards a less immunosuppressive phenotype. Myeloid-derived suppressor cells and tumour-associated macrophages are major components of the immunosuppressive microenvironment and as a result promote tumour growth and favour angiogenesis and metastasis formation. Growing evidence indicates that tasquinimod targets these myeloid cells and modulates local tumour immunity by blocking the interaction between the multifunctional protein S100A9 and its ligands receptor of advanced glycation end products and Toll-like receptor 4. Its anti-angiogenic effects are achieved at least in part through these effects on regulatory myeloid cells and also potentially through inactivating histone deacetylase-4 and reducing expression of hypoxia-inducible factor 1-controlled genes. The aim is to comprehensively review the mode of action of tasquinimod as a novel oral anti-cancer agent. Based on its unique combination of effects, tasquinimod is a novel agent with clinical therapeutic potential in various solid tumours, both alone and as part of rational combination therapy.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Fingerprint

Tumor Microenvironment
Tumors
Myeloid Cells
Neoplasms
Immunosuppressive Agents
Calgranulin B
Neoplasm Metastasis
Hypoxia-Inducible Factor 1
Toll-Like Receptor 4
Histone Deacetylases
Mouth Neoplasms
Growth
tasquinimod
Macrophages
Immunity
Ligands
Phenotype
Genes
Cells
Therapeutics

Keywords

  • Myeloid-derived suppressor cell
  • Quinoline carboxamide
  • S100A9
  • Tasquinimod
  • Tumour microenvironment
  • Tumour-associated macrophage

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Mechanisms of action of tasquinimod on the tumour microenvironment. / Raymond, E.; Dalgleish, A.; Damber, J. E.; Smith, M.; Pili, Roberto.

In: Cancer Chemotherapy and Pharmacology, Vol. 73, No. 1, 01.2014, p. 1-8.

Research output: Contribution to journalReview article

Raymond, E. ; Dalgleish, A. ; Damber, J. E. ; Smith, M. ; Pili, Roberto. / Mechanisms of action of tasquinimod on the tumour microenvironment. In: Cancer Chemotherapy and Pharmacology. 2014 ; Vol. 73, No. 1. pp. 1-8.
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