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Targeting Angiogenesis in Colorectal Carcinoma

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Abstract

Neo-angiogenesis plays a key role in colorectal cancer, with the vascular endothelial growth factor family proteins and their receptors in particular triggering multiple signaling networks that result in endothelial cell survival, migration, mitogenesis, differentiation, and vascular permeability. Anti-angiogenic therapies have improved colorectal cancer prognosis within the past 15 years. Bevacizumab demonstrated efficacy in combination with chemotherapy under different conditions, including as first- and second-line therapies, and also as a maintenance treatment strategy. Other drugs targeting angiogenesis effectors (e.g., ramucirumab and aflibercept) were approved after bevacizumab failure, confirming the concept of “continuous anti-angiogenic blocking”. Recently, a number of new orally available multiple receptor tyrosine kinase inhibitors have been tested in late-stage clinical trials, with modest efficacy. Due to the availability of several anti-angiogenic agents, we need well-designed prospective randomized trials to optimize therapeutic sequencing. The place of biosimilars in the therapeutic armamentarium remains unclear at the moment. Further research is warranted to identify robust predictive biomarkers of efficacy and innovative clinically meaningful anti-angiogenic drugs that are cost-efficient.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Anthony Lopez, Kazuto Harada, Maria Vasilakopoulou, Namita Shanbhag & Jaffer A. Ajani

  2. Department of Gastroenterology and Hepatology and Inserm U954, Nancy University Hospital, Lorraine University, 5 allée du Morvan, 54511, Vandoeuvre-lès-Nancy, France

    Anthony Lopez

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Correspondence to Jaffer A. Ajani.

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Conflict of interest

Anthony Lopez has received research funding from Roche, has served as consultant for Amgen, received lecture fees from Vifor Pharma, and received travel accommodation expenses (not for this work) from Abbvie, Amgen, MSD, Vifor-Pharma. Jaffer A. Ajani has received honoraria from Lilly, Bayer, Novartis, Five Prime Therapeutics, Taiho Pharmaceutical, Genentech, and Roche, received research funding from Novartis, Bristol-Myers Squibb, Taiho Pharmaceutical, Roche/Genentech, MedImmune, Amgen, Lilly/ImClone, Merck, Delta-Fly Pharma, Gilead Sciences, and Takeda, and received travel accommodation expenses (not for this work) from Novartis, Bayer, and Five Prime Therapeutics. Kazuto Harada, Maria Vasilakopoulou, and Namita Shanbhag declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Lopez, A., Harada, K., Vasilakopoulou, M. et al. Targeting Angiogenesis in Colorectal Carcinoma. Drugs 79, 63–74 (2019). https://doi.org/10.1007/s40265-018-1037-9

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