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Antiangiogenic therapy in human gastrointestinal malignancies
  1. J Heidemann1,
  2. D G Binion2,
  3. W Domschke1,
  4. T Kucharzik1
  1. 1Department of Medicine B, University of Münster, Münster, Germany
  2. 2Department of Internal Medicine, Division of Gastroenterology/Hepatology, Medical College of Wisconsin, Milwaukee, USA
  1. Correspondence to:
    Dr J Heidemann
    Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany; jan_heidemann{at}hotmail.com

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SUMMARY

Angiogenesis is a crucial process involved in numerous physiological and pathophysiological settings. During the past three decades, the field of tumour associated angiogenesis has been the focus of a plethora of basic research projects and clinical studies. Tumour associated neovessels satisfying the increased demand of oxygen and nutrients in malignant tumours are now emerging as specific targets for novel antineoplastic agents. This article discusses the present data on antiangiogenic treatment of human gastrointestinal malignancies, including gastric, pancreatic, and colorectal adenocarcinoma, and outlines potential future perspectives, such as development of surrogate markers of angiogenesis.

PROCESS OF TUMOUR ANGIOGENESIS

Angiogenesis, the formation of new vessels from existing capillary beds, represents a central mechanism involved in many physiological and pathophysiological conditions, including embryonal development, wound healing, and chronic inflammation.1 In malignant tumours, angiogenesis represents a prerequisite for tumour growth, as the high metabolism of tumour cells requires large amounts of oxygen and nutrients. Without angiogenesis, the growth of malignant tumours is limited to 1–2 mm in diameter, which corresponds to the maximum distance oxygen can diffuse.2,3 Tumour vascularisation represents a conditio sine qua non for exponential tumour growth. Studies have indicated that the mitotic index of tumour cells decreases with increasing distance from the supplying microvessel.1,3,4 Primary tumours as well as their metastases are dependent on tumour associated microvessels to establish an independent blood supply.3,5 Enhanced vascularity allows tumours not only to expand in size but also facilitates haematogenous spreading by a higher probability of tumour angioinvasion. Once deposited in a distant organ, tumour metastases are dependent on building their own microvasculature.6 For this reason, disruption of angiogenesis pathways provides a therapeutic perspective in the treatment of primary malignant human tumours as well as their metastases.

The concept that metastases are solely dependent on newly formed blood vessels …

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