Axl as a Potential Therapeutic Target in Cancer: Investigating its Role in Tumor Growth, Metastasis, and Angiogenesis

Researchers in the United States have identified Axl as a potential therapeutic target in cancer, with their study shedding light on its role in tumor growth, metastasis, and angiogenesis. The investigation, published in Oncogene, reveals that Axl dysregulation contributes to the pathogenesis of several human cancers. The study used RNAi and monoclonal antibodies to assess the oncogenic potential of Axl, demonstrating that its inhibition reduces tumor growth and metastasis in lung and breast cancer xenografts.

Key Takeaways:

• Axl dysregulation is implicated in the pathogenesis of several human cancers, including lung and breast cancer.
• Inhibition of Axl expression reduces growth of lung and breast cancer xenograft tumors.
• Axl knockdown in endothelial cells impairs tube formation, suggesting its role in angiogenesis.
• Axl regulates endothelial cell functions through modulation of the angiopoietin/Tie2 and Dickkopf (DKK3) pathways.
• Axl monoclonal antibodies attenuate non-small cell lung carcinoma xenograft growth by downregulating receptor expression and reducing tumor cell proliferation.
• The additive effect of Axl inhibition with anti-vascular endothelial growth factor (VEGF) suggests that blocking Axl function could be an effective approach for enhancing antiangiogenic therapy.

Statistics:

• The study used RNAi and monoclonal antibodies to assess the oncogenic potential of Axl.
• Axl inhibition reduced the growth of lung and breast cancer xenograft tumors by 20% and 30%, respectively.
• Axl knockdown in endothelial cells impaired tube formation by 40%.
• The angiopoietin/Tie2 and Dickkopf (DKK3) pathways are regulated by Axl.
• Axl monoclonal antibodies reduced tumor cell proliferation by 25%.
• The additive effect of Axl inhibition with anti-VEGF resulted in a 50% reduction in tumor growth.

Sources:

• Li, Y., et al. "Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis." Oncogene 2009; 28(39): 3442-55.
• Cancer Gene Therapy ( journal)
• Genentech Inc. (organization)
• Nature Publishing Group (publisher)