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Antiangiogenic
therapy of experimental cancer does not induce acquired drug resistance
Boehm
T, Folkman J, Browder T, O'Reilly MS
Department
of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA. boehmvt@a1.tch.harvard.edu
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.
PMID:
9389480 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9389480&dopt=Abstract
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