Transcriptional anti-angiogenesis therapy of human pancreatic cancer.
Pancreatic cancer angiogenesis has been attributed to genetic and epigenetic alterations (e.g., oncogene activation and suppressor inactivation) and a chaotic tumor microenvironment (e.g., hypoxia, acidosis, free radical stress and imbalanced growth factor production). Those diverse "upstream signal" factors appear to converge their signaling pathways on limited sets of nuclear transcription factors (e.g., Sp1, Stat3 and NF-kappaB). Aberrant activities of these factors confer a tremendous survival and growth advantage to existing and/or emerging malignant cells through alteration of the expression and functions of their diverse "downstream effector" factors (e.g., VEGF and IL-8). Therefore, targeting a single transcription factor can affect the malignant phenotype more profoundly than just targeting any single upstream signal and/or downstream effector factor.
Xie
Keping
K
Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. kepxie@mail.mdanderson.org
Wei
Daoyan
D
Huang
Suyun
S
D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D014157:Transcription Factors