Abstract：
:TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sensitivity to TER286 over their parental lines in parallel with increased expression of GST P1-1. In primary human tumor clonogenic assays, the spectrum of cytotoxic activity observed for TER286 was both broad and unusual when compared to a variety of current drugs. In murine xenografts of M7609 engineered to have high, medium, or low GST P1-1, responses to TER286 were positively correlated with the level of P1-1. Cytotoxicity was also observed in several other cell culture and xenograft models. In xenografts of the MX-1 human breast carcinoma, tumor growth inhibition or regression was observed in nearly all of the animals treated with an aggressive regimen of five daily doses. This schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to 60% of control and was no worse than for a single dose of TER286. These studies have motivated election of TER286 as a clinical candidate.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Morgan AS,Sanderson PE,Borch RF,Tew KD,Niitsu Y,Takayama T,Von Hoff DD,Izbicka E,Mangold G,Paul C,Broberg U,Mannervik B,Henner WD,Kauvar LMsubject
Has Abstractpub_date
1998-06-15 00:00:00pages
2568-75issue
12eissn
0008-5472issn
1538-7445journal_volume
58pub_type
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