Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo
Gutman, M.; Szold, A.; Ravid, A.; Lazauskas, T.; Merimsky, O.; Klausner, J.M.
Anticancer Research 16(6b): 3673-3677
1996
ISSN/ISBN: 0250-7005 PMID: 9042240 Document Number: 461389
Thalidomide was recently suggested to be an angiogenesis-inhibitor following the demonstration of its activity in a rabbit cornea micropocket model. The purpose of the present study was to test its efficacy in solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells were injected subcutaneously, intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg thalidomide starting either two or 10 days following tumor cell injection. The tumors were measured and compared with controls. There was no growth retardation in CT-26 beating mice nor in mice with pulmonary or peritoneal metastases of B16-F10 melanoma. In 317 groups of mice with SC B16-F10 tumors, growth retardation was demonstrated, however the difference was not statistically significant. All tumors eventually reached maximal size, similar to controls. Morphological evaluation of the blood vessels oriented towards the tumor revealed that in both thalidomide and control groups, all mice had developed an intact network of new blood vessels. In our model for the oral administration of thalidomide inhibition of tumor growth and angiogenesis did not occur. We hypothesize that the lack of sustained antiangiogenic response was either due to immune modulation or to tumor heterogeneity and adaptation.