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Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors

Rachel M A Linger1, Amy K Keating, H Shelton Earp

  • 1University of Colorado Denver School of Medicine, Department of Pediatrics, Aurora, CO 80045, USA.

Expert Opinion on Therapeutic Targets
|September 3, 2010
PubMed
Abstract

Insights

Axl and Mer receptor tyrosine kinases drive cancer progression and chemoresistance. Inhibiting these targets shows promise for anti-tumor and anti-metastatic therapies, especially combined with chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Axl and Mer receptor tyrosine kinases (RTKs) are linked to poor cancer prognosis.
  • Their roles in cancer development and progression were previously unclear.
  • RTKs like Axl and Mer influence cancer cell survival, migration, invasion, metastasis, and chemosensitivity.

Purpose of the Study:

  • To review Axl and Mer signaling pathways in cancer.
  • To examine evidence for Axl and Mer as therapeutic targets in glioblastoma, NSCLC, and breast cancer.
  • To discuss developing Axl and Mer inhibitors.

Main Methods:

  • Summarized Axl and Mer signaling pathways in cancer cells.
  • Examined evidence validating Axl and Mer as therapeutic targets.
  • Reviewed Axl and Mer inhibitors currently in development.

Main Results:

  • Addressed potential toxicities of Axl or Mer inhibition.
  • Proposed that inhibitors targeting the tumor microenvironment offer a dual therapeutic approach.
  • Highlighted the potential to target tumor cells and stromal components.

Conclusions:

  • Axl and Mer RTKs mediate multiple oncogenic phenotypes.
  • RTK activation is a mechanism of chemoresistance in solid tumors.
  • Targeted inhibition may be effective anti-tumor and anti-metastatic therapy, especially with cytotoxic treatments.

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