Does Axl have potential as a therapeutic target in pancreatic cancer?

Expert Opin Ther Targets. 2018 Nov;22(11):955-966. doi: 10.1080/14728222.2018.1527315. Epub 2018 Oct 3.

Abstract

Pancreatic cancer is a leading cause of cancer-related death. Metastasis, therapy resistance, and immunosuppression are dominant characteristics of pancreatic tumors. Strategies that enhance the efficacy of standard of care and/or immune therapy are likely the most efficient route to improve overall survival in this disease. Areas covered: Axl, a member of the TAM (Tyro3, Axl, MerTK) family of receptor tyrosine kinases, is involved in cell plasticity, chemoresistance, immune suppression, and metastasis in various cancers, including pancreatic cancer. This review provides an overview of Axl and its function in normal conditions, summarizes the regulation and function of Axl in cancer, and highlights the contribution of Axl to pancreatic cancer as well as its potential as a therapeutic target. Expert opinion: Axl is an attractive therapeutic target in pancreatic cancer because it contributes to many of the roadblocks that hamper therapeutic efficacy. Clinical evidence supporting Axl inhibition in pancreatic cancer is currently limited; however, multiple clinical trials have been initiated or are in the planning phase to test the effect of inhibiting Axl in conjunction with standard therapy in pancreatic cancer patients. We anticipate that these studies will provide robust validation of Axl as a therapeutic target in pancreatic cancer.

Keywords: Axl; epithelial plasticity; immunosuppression; metastasis; pancreatic cancer; therapy resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Axl Receptor Tyrosine Kinase
  • Drug Resistance, Neoplasm
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human