Biomarkers for Therapies Directed at Angiogenesis

Since 2004, six drugs with antiangiogenic properties—bevacizumab, sorafenib, sunitinib, pazopanib, temsirolimus, and everolimus—have been approved for clinical use in patients with advanced solid tumors, on the basis of their capacity to improve survival in phase 3 studies. Despite this enthusiasm in having these drugs approved, no significant predictive or prognostic factors have been identified for better patient selection with the aim of increasing the likelihood of clinical benefit. Biomarkers are understood as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Different kinds of biomarkers are available for clinical practice, including prognostic biomarkers associated with the risk of disease development, spread, or aggressiveness or with survival rates, as well as predictive biomarkers that provide us with information on the efficacy of a particular therapeutic option. Currently, several potential biomarkers have emerged from recently completed phase 1, 2, and 3 studies. These biomarkers are extensive in origin, depending on the source of the specimen (blood, serum, tumor tissue, circulating tumor cells, surrogate tissue), the type of analysis being done on the specimen (genomic—DNA or RNA—or proteomic), and sometimes whether the biomarker comes from clinical or radiologic data. Unfortunately, no validated predictive biomarkers of angiogenesis or antiangiogenesis are available for routine clinical use. Future anticancer drug research should run parallel to an ambitious biomarker development program to facilitate the selection of patients who would benefit most from these new targeted therapies, thereby providing more accurate benefit/safety and benefit/cost relationships.