Radiotherapy and antiangiogenic TM in lung cancer.
Tetrathiomolybdate (TM) is a potent nontoxic orally delivered copper complexing agent under development for the last several years for the treatment of Wilson's disease. It has been shown to block angiogenesis in primary and metastatic tumors. Therefore, the combination of cytotoxic radiotherapy (RT) and antiangiogenic TM could target both the existing tumor and the tumor microvasculature in a comprehensive strategy. Using a Lewis lung high metastatic (LLHM) carcinoma mouse tumor model, we demonstrate that the combination of TM and RT is more effective than either used as monotherapy. We also show that their therapeutic effects are additive, with no additional toxicity. We show that TM has no significant cytotoxicity in vitro against LLHM tumor cells, further supporting the antiangiogenic mechanism for its action.
Khan
Mohamed K
MK
Department of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI 48109-0936, USA. mokhan@umich.edu
Miller
Meredith W
MW
Taylor
Jeremy
J
Gill
Navkiranjit K
NK
Dick
Robert D
RD
Van Golen
Kenneth
K
Brewer
George J
GJ
Merajver
Sofia D
SD
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008982:Molybdenum / Q000627:therapeutic use*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011878:Radiotherapy; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D008982:Molybdenum; C020809:tetrathiomolybdate; C022616:thiazolyl blue