Effect of p53 Status on Tumor Response to Antiangiogenic Therapy

• Published in: Science (American Association for the Advancement of Science) Vol. 295; no. 5559; pp. 1526 - 1528
• Main Authors: Yu, Joanne L., Rak, Janusz W., Coomber, Brenda L., Hicklin, Daniel J., Kerbel, Robert S.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 22.02.2002; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Angiogenesis inhibitors; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antibodies - therapeutic use; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Biological and medical sciences; Biology; Cancer; Cancer cells; Care and treatment; Cell Hypoxia; Cell Survival; Cells; Chemotherapy; Colorectal Neoplasms; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - genetics; Cyclins - metabolism; Drug therapy; Drugs; Endothelial cells; Exons; Gene Deletion; Gene Silencing; Genes, p53; Genetic aspects; Genetics; Genomics; HCT116 cells; Humans; Hypoxia; In Situ Nick-End Labeling; Medical sciences; Mice; Mice, SCID; Narcotics; Neoplasm Transplantation; Neoplasms, Experimental - blood supply; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Pharmacology. Drug treatments; Polymerase chain reaction; Receptor Protein-Tyrosine Kinases - immunology; Receptors, Growth Factor - immunology; Receptors, Vascular Endothelial Growth Factor; Therapy; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - metabolism; Tumors; Vinblastine - therapeutic use; Canada; United States; Antineoplastic agent; Cell proliferation; Human origin; Animal model; Rodentia; Biological activity; Symptomatology; Vertebrata; Sensitivity; Mammalia; TP53 Gene; Treatment; Mouse; Animal; Established cell line; Genetics; Antiangiogenic agent; Tumor suppressor gene
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1068327

The p53 tumor suppressor gene is inactivated in the majority of human cancers. Tumor cells deficient in p53 display a diminished rate of apoptosis under hypoxic conditions, a circumstance that might reduce their reliance on vascular supply, and hence their responsiveness to antiangiogenic therapy. Here, we report that mice bearing tumors derived from p53-/-HCT116 human colorectal cancer cells were less responsive to antiangiogenic combination therapy than mice bearing isogenic p53+/+tumors. Thus, although antiangiogenic therapy targets genetically stable endothelial cells in the tumor vasculature, genetic alterations that decrease the vascular dependence of tumor cells can influence the therapeutic response of tumors to this therapy.