AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations

Int J Mol Sci. 2020 Nov 10;21(22):8419. doi: 10.3390/ijms21228419.

Abstract

Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials.

Keywords: AXL; biomarkers; breast cancer; immunotherapy; targeted therapy; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Axl Receptor Tyrosine Kinase
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / physiology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / physiopathology*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / physiology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human