XL184

XL184 is a small molecule designed to inhibit multiple receptor tyrosine kinases, specifically MET and VEGFR2. MET is a receptor tyrosine kinase that plays key roles in cellular proliferation, migration, and invasion as well as angiogenesis1. These biological processes contribute to the transformation, progression, survival and metastasis of cancer cells1. The MET pathway is frequently activated in tumors through MET amplification, mutation, and overexpression, as well as through overexpression of its ligand HGF1.  Expression of VEGF has been observed in a variety of cancers and has been associated with the stimulation and growth of new blood vessels to support the tumor2,3. MET and VEGFR2 are important driving forces in angiogenesis, implicated in the ability of tumors to overcome hypoxia following angiogenesis inhibition4,5.

Related Clinical Trials

Phase Clinical Trial Status
Phase 3 Efficacy Study of XL184 in Adults With Medullary Thyroid Cancer Recruiting
Phase 2 Study of XL184 in Adults With Glioblastoma Multiforme Recruiting
Phase 2 Study of XL184 in Adults With Advanced Malignancies Recruiting
Phase 1b/2 A Study of XL184 With or Without Erlotinib in Adults With Non-Small Cell Lung Cancer Recruiting
Phase 1 Safety Study of XL184 in Combination With Temozolomide and Radiation Therapy in the Initial Treatment of Adults With Glioblastoma Recruiting
Phase 1 Study of XL184 in Adults With Advanced Malignancies Closed for new recruitment

 

  1. Christensen JG, Burrows J, Salgia R.  c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention.  Cancer Lett.  2005; 225(1):1-26.
  2. Sandler A.  Bevacizumab in non-small cell lung cancer.  Clin Cancer Res.  2007; 13 (15 Suppl): 4613s-4616s.
  3. Heath VL and Bicknell R. Anticancer strategies involving the vasculature. Nat Rev Clin Oncol. 2009; Jul;6(7):395-404.
  4. You WK and McDonald DM. The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. BMB Reports. 2008; 41:833–839.
  5. Schmidt C. Why do tumors become resistant to antiangiogenesis drugs? J. Natl. Cancer. Inst. 2009;101:1530–1532.