title: Targeting Axl and Mer kinases in cancer.
abstract: Receptor tyrosine kinases (RTK) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play an important role in signal transduction in both normal and malignant cells. The mammalian TAM RTK family includes 3 closely related members: Tyro-3, Axl, and Mer. Overexpression or ectopic expression of the TAM receptors has been detected in a wide array of human cancers. Growth arrest-specific gene 6 has been identified as the major ligand for these TAM RTKs, and its binding to the receptors has been shown to promote proliferation and survival of cancer cells in vitro. Abnormal expression and activation of Axl or Mer can provide a survival advantage for certain cancer cells. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and would potentially be a therapeutic strategy to target cancer cells. This review elucidates the role of Axl and Mer in normal cellular function and their role in oncogenesis. In addition, we review the potential to inhibit these RTKs for the development of therapeutic targets in treatment of cancer.
authors.affiliation: Pediatric Hematology/Oncology, Primary Children's Medical Center, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. anupam.verma@hsc.utah.edu
authors.forename: Anupam
authors.initials: A
authors.lastname: Verma
authors.forename: Steven L
authors.initials: SL
authors.lastname: Warner
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Vankayalapati
authors.forename: David J
authors.initials: DJ
authors.lastname: Bearss
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase