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From early literature exploring central research questions to today's most cited review articles, the history of research on VEGF in angiogenesis in tumor biology is marked by a number of seminal papers.

The first in vivo images of tumor angiogenesis¹

Ide AG, Baker NH, Warren SL. Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Roentgenol. 1939;42:891-899.

Original image from Ide et al (1939) showing an extensive vascular network in transplanted rabbit epithelioma.¹

The first quantitative assessment of vascular growth²

Algire GH, Chalkley HW, Legallais FY, Park HD. Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst. 1945;6:73-85.

Original figure from Algire et al (1945) depicting vascular development in a mammary-gland carcinoma. Reproduced with permission from the Journal of the National Cancer Institute.²

Folkman's extraordinary hypothesis³

Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med. 1971;133:275-288.

Original figure from Folkman et al (1971) depicting how tumors acquire vital nutrients in both prevascular and vascular states. Here, tumor angiogenesis factor (TAF) is hypothesized to be responsible for this transformation. Reproduced with permission from the Journal of Experimental Medicine.^3,4

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182-1186.

In this seminal paper, Judah Folkman inaugurated the modern age of angiogenesis research by postulating that the process of angiogenesis could be targeted as a way to inhibit the growth of solid tumors.⁵

Initial cloning of VEGF⁶

Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161:851-858.

The most cited* review article on angiogenesis⁷

Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1:27-31.

*As noted by Thomson Scientific on www.esi-topics.com/angiogenesis/papers/map.html. Accessed October 19, 2011.

Other suggested readings

Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029-1039.

Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun. 1989;161:851-858.

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182-1186.

Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011-1027.

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.

References:

1.

Ide AG, Baker NH, Warren SL. Am J Roentgenol. 1939;42:891-899.

2.

Algire GH, Chalkley HW, Legallis FY, Park HD. J Natl Cancer Inst. 1945;6:73-85.

3.

Folkman J, Merler E, Abernathy C, Williams G. J Exp Med. 1971;133:275-288.

4.

Ferrara N. Nat Rev Cancer. 2002;2:795-803.

5.

Folkman J. N Engl J Med. 1971;285:1182-1186.

6.

Ferrara N, Henzel WJ. Biochem Biophys Res Commun. 1989;161:851-858.

7.

Folkman J. Nat Med. 1995;1:27-37.