Targeting angiogenesis in pancreatic cancer: rationale and pitfalls.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer responsible for over 20% of deaths due to gastrointestinal malignancies. PDAC is usually diagnosed at an advanced stage which, in part, helps to explain its high resistance to chemotherapy and radiotherapy. In addition, the cancer cells in PDAC have a high propensity to metastasize and to aberrantly express several key regulators of angiogenesis and invasion. Chemotherapy has only provided a modest impact on mean survival and often induces side effects. Targeting angiogenesis alone or in combination with other modalities should be investigated to determine if it may provide for increased survival.


METHODS
This review summarizes the alterations in PDAC that play a critical role in angiogenesis and provides an overview of current and therapeutic strategies that may be useful for targeting angiogenesis in this malignancy.
Whipple
Chery
C
Department of Medicine, Dartmouth Hitchcock Medical Center and Dartmouth Medical School, Hanover, NH, USA.
Korc
Murray
M
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000098:blood supply* / Q000188:drug therapy*; D015687:Cell Hypoxia / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D004359:Drug Therapy, Combination; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A