Cited by 1,683Angiogenesis and VEGF in CancerCancer Cells and MetastasisMathematical Biology Tumor Growth

Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance

Boehm, Thomas, Folkman, Judah, Browder, Timothy, O'Reilly, Michael S.·1997·Nature

Abstract

Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States, many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells. In contrast, endothelial cells are genetically stable, homogeneous and have a low mutational rate. Therefore, antiangiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance. Endostatin, a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy. These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor. An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy.

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Crossref · 10.1038/37126

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  • Angiogenesis plays a critical role in tumor growth and metastasis formation, and blocking angiogenesis prevents tumor growth and forces regression of existing lesions.

    “Angiogenesis plays a critical role in tumor growth and metastasis formation, and blocking angiogenesis prevents tumor growth and forces regression of existing lesions (59)(60)(61).”

    From Adipose tissue remodeling and obesity (2011) · cites this paper as [59]

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Authors
Boehm, T., Folkman, J., Browder, T., & O'Reilly, M. S.
Affiliations
  • Harvard University (US)
  • Dana-Farber/Harvard Cancer Center (US)
Corresponding author
Boehm, Thomas
Venue
Nature
Published
1997-11
Volume
390
Issue
6658
Pages
404-407
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1579297325
Cited by
1,683
References
12
Citations by year
2026: 1 · 2025: 4 · 2024: 11 · 2023: 19 · 2022: 9 · 2021: 19 · 2020: 16 · 2019: 18 · 2018: 15 · 2017: 24 · 2016: 35 · 2015: 25 · 2014: 30 · 2013: 48 · 2012: 47
FWCI
40.79
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
Keywords
anti-angiogenic therapy, acquired drug resistance, endostatin, angiogenesis inhibitors, tumor dormancy, Lewis lung carcinoma, B16F10 melanoma, tumor recurrence, endothelial cells, tumor heterogeneity
MeSH terms
Animals, Antineoplastic Agents, Collagen, Cyclophosphamide, Fibrosarcoma, Melanoma, Experimental, Mice, Inbred C57BL, Neoplasm Recurrence, Local, Neoplasm Transplantation, Neoplasms, Experimental, Neovascularization, Pathologic, Peptide Fragments, Carcinoma, Lewis Lung, Drug Resistance, Neoplasm, Endostatins, Mice

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