Tumor and Host-Mediated Pathways of Resistance and Disease Progression in Response to Antiangiogenic Therapy

• Published in: Clinical cancer research Vol. 15; no. 16; pp. 5020 - 5025
• Main Authors: EBOS, John M. L, LEE, Christina R, KERBEL, Robert S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-08-2009
• Subjects: Angiogenesis Inhibitors - therapeutic use; Antineoplastic agents; Biological and medical sciences; Disease Progression; Drug Resistance, Neoplasm - genetics; Humans; Medical sciences; Models, Biological; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Pharmacology. Drug treatments; Signal Transduction - drug effects; Signal Transduction - genetics; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - genetics; Resistance; Treatment; Malignant tumor; Disease; Antiangiogenic agent; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-0095

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. (Clin
Cancer Res 2009;15(16):5020–5)