The Use of Orthotopic Models to Validate Antivascular Therapies for Cancer

Abstract

The growth and survival of malignant tumors are dependent on an adequate vascular supply. A growing body of preclinical evidence suggests that therapeutic targeting of tumor-associated blood vessels may be an effective means to control tumor growth and limit metastatic spread. Unfortunately, the success of vascular targeting approaches for the treatment of human cancer has been less than remarkable. One likely explanation for the discrepancy between the preclinical findings and results observed in patients is related to the tumor models utilized in preclinical studies. Indeed, most reports seeking to validate the use of antivascular agents for the treatment of cancer have drawn conclusions from tumors implanted into the subcutaneous space and thus have neglected to account for the impact of the specific organ microenvironment on the regulation of tumor growth. While it is difficult to replicate several facets of human tumor growth using animal models, microenvironmental concerns may be easily addressed through the use of orthotopically implanted tumors. Differences between orthotopic and ectopic models are considered, and advances in antivascular therapy for cancer are discussed.