Targeting angiogenic pathways involving tumor-stromal interaction to treat advanced human prostate cancer.
Interfering with and preventing tumor angiogenesis is an attractive therapeutic approach for treating cancer metastases. This commentary presents treatment strategies that may enhance the effectiveness of anti-angiogenic therapy by selectively targeting newly sprouting and immature vessels, inhibiting the production of angiogenic factors, and disrupting extracellular matrices. We propose several clinical paradigms, including hormonal ablation, intermittent androgen suppression, chemotherapy, and radiation therapy, that 'injure' nascent vasculature and interrupt the cancer cell-stromal relationship, thereby potentiating the efficacy of experimental anti-angiogenic agents. These stromal-epithelial interactions play an important role in the development, proliferation and dissemination of prostate cancer, as well as guiding the processes of tumor neovascularization. Successful utilization and targeting of tumor angiogenesis requires an increased understanding of tumor cell-stromal cell-endothelial cell relationships, most notably the intricate intracellular signalling cascades mediated by growth factors and the extracellular matrix.
Sokoloff
M H
MH
Department of Urology, University of Virginia, Charlottesville, USA.
Chung
L W
LW
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002450:Cell Communication; D003131:Combined Modality Therapy; D016228:Endothelial Growth Factors / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016588:Anticarcinogenic Agents; D016228:Endothelial Growth Factors; D016023:Integrins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors