Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy.
Despite early benefits seen in cancer patients treated with antivascular endothelial growth factor (VEGF) pathway-targeted drugs, the clinical benefits obtained in terms of progression-free or overall survival have been more modest than expected. This outcome is, at least in part, due to antiangiogenic drug resistance mechanisms that involve pathways mediated largely by the tumor, whether intrinsic or acquired in response to therapy, or by the host, which is either responding directly to therapy or indirectly to tumoral cues. The focus of this review is to distinguish, where possible, between such host and tumor-mediated pathways of resistance and discuss key challenges facing the preclinical and clinical development of antiangiogenic agents, including potential differences in drug efficacies when treating primary tumors or various stages of metastatic disease.
Ebos
John M L
JM
Sunnybrook Health Sciences Centre Molecular and Cellular Biology Research, Toronto, Ontario, Canada.
Lee
Christina R
CR
Kerbel
Robert S
RS
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A