New approaches in angiogenic targeting for colorectal cancer.
TLDR
Current and future approaches in angiogenic targeting for CRC are discussed and present a strong medical need for more effective and well-tolerated therapies.Abstract:
Colorectal carcinoma (CRC) is one of the leading causes of cancer death worldwide. In the last decade, the addition of irinotecan and oxaliplatin to standard fluorouracil-based chemotherapy regimens have set the new benchmark of survival for patients with metastatic CRC at approximately 20 mo. Despite these advances in the management of CRC, there is a strong medical need for more effective and well-tolerated therapies. The dependence of tumor growth and metastasis on blood vessels makes angiogenesis a rational target for therapy. One of the major pathways involved in this process is the vascular endothelial growth factor (VEGF) and its receptors (VEGFR). In 2004, the first agent targeting angiogenesis, bevacizumab (BV), was approved as an adjunct to first-line cytotoxic treatment of metastatic CRC. The role of BV as part of adjuvant treatment and in combination with other targeted therapies is the subject of ongoing trials. However, BV is associated with an increase in the risk of arterial thromboembolic events, hypertension and gastrointestinal perforations and its use must be cautious. Novel VEGFR TK inhibitors with different ranges of nanomolar potencies, selectivities, and pharmacokinetic properties are entering phase III trials for the treatment of cancer. Conversely, one of these novel agents, vatalanib, has been shown not to confer survival benefit in first and second-line treatment of advanced CRC. The basis of these findings is being extensively evaluated. Ongoing and new well-designed trials will define the optimal clinical application of the actual antiangiogenic agents, and, on the other hand, intensive efforts in basic research will identify new agents with different antiangiogenic approaches for the treatment of CRC. In this review we discuss and highlight current and future approaches in angiogenic targeting for CRC.read more
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Anticancer strategies involving the vasculature
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Investigation of the effects of curcumin on serum cytokines in obese individuals: a randomized controlled trial.
Shiva Ganjali,Amirhossein Sahebkar,Elahe Mahdipour,Khadijeh Jamialahmadi,Sepideh Torabi,Saeed Akhlaghi,Gordon A. Ferns,Seyed Mohammad Reza Parizadeh,Majid Ghayour-Mobarhan +8 more
TL;DR: The findings of the present trial suggested that curcumin may exert immunomodulatory effects via altering the circulating concentrations of IL-1β, IL-4, and VEGF.
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Curcumin Inhibits VEGF Mediated Angiogenesis in Human Intestinal Microvascular Endothelial Cells Through COX-2 and MAPK Inhibition
TL;DR: An important role for COX-2 in the regulation of angiogenesis in HIMECs via MAPKs is demonstrated, suggesting that this natural product possesses antiangiogenic properties, which warrants further investigation as adjuvant treatment of IBD and cancer.
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Role of Cancer Microenvironment in Metastasis: Focus on Colon Cancer
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TL;DR: The aim of this manuscript is to review how the cancer microenvironment influences the journey of a metastatic cell taking liver invasion by colorectal cancer cells as a model.
References
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A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal Cancer
Richard M. Goldberg,Daniel J. Sargent,Roscoe F. Morton,Charles S. Fuchs,Ramesh K. Ramanathan,Stephen K. Williamson,B. Findlay,Henry C. Pitot,Steven R. Alberts +8 more
TL;DR: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe and should be considered as a standard therapy for patients with advanced colorectal cancer.