Cancer Institute , antitumor

Venditti JM. The National Cancer Institute antitumor drug discovery program, current and future perspectives A commentary. Cancer Treat Rep 1983 67 767-772. 

The antineoplastic agent mitindomide (160) in fact represents the well-known product from irradiation of maleimide in benzene [30]. The activity of this old compound was uncovered by one of the large antitumor screens maintained by the National Cancer Institute, The structure is sufficiently complex and the starting materials sufficiently available to lead one to suspect that the product is still produced photochemically. The product can be rationalized by assuming successive 1,4 and 1,2 additions to benzene. Intermediate 159a involves the 1,4 followed by 1,2 addition intermediate 159b presupposes the steps occur in the reverse order. 

Pharmacological activity has been studied for about 40 T. alkaloids. Some of these have been studied during a plant antitumor screening program carried out under the auspices of the National Cancer Institute of the U.S. National Institute... 

The approval of Taxol for marketing in December 1992 was the culmination of 35 years of work. During this period of time the National Cancer Institute (NCI) and the U.S. Department of Agriculture (USDA) collaborated to collect, identify, and screen U.S. native plant material for antitumor activity. The year 1992 also marked, coincidentally, the discovery of the Ice Man in the Italian Alps. This Bronze Age man, who died 5300 years ago, was found in possession of a pure copper axe set in a yew wood handle and an unfinished 6-foot yew bow. Obviously, the yew tree has played a number of important roles for humans throughout history. 

The discovery of Taxol is a fruit of a National Cancer Institute (NCI)-sponsored project on identification of antitumor agents from natural resources. Bioassay-guided fractionation led to the isolation of this unique compound from Taxus bre-vifolia (pacific yew). Wani et al. also identified another famous antitumor natural product camptothecin. Unlike camptothecin, which was abandoned in the phase of clinical trial because of its severe toxicity, Taxol was almost discarded at the preliminary phase because it only exhibited moderate in vitro activity toward P388, a murine leukemia cell line that was used in the standard evaluation system by NCI researchers at that time. However, it was rescued by a subsequent finding of its strong and selective antitumor activities toward several solid tumors, and more... 

This investigation was supported by grants from the National Cancer Institute, the National Institutes of Health (NIH) (CA-17625), and the National Institute of Allergy and Infectious Diseases, NIH (AI-33066) that were awarded to K.H. Lee. This article is No. 257 in the series Antitumor Agents and No. 71 20. 

Much of the current work on tylophorine alkloids was prompted by their profound antitumor activity. Evaluation of tylophorine (1) and related analogs in the National Cancer Institute s antitumor screen showed a uniform and potent growth inhibitory effect (average GT50 = 10 M) against all 60 cell lines, with notable selectivity toward several refractory cell lines, including melanoma and lung tumor cell lines [77]. 

An earlier paper (1 ) described a method for estimating the probability of activity of compounds. In that report the method was applied to a small set of data for the purpose of comparing the performance to that of more sophisticated pattern recognition methods. The intended application was the large volume of data from the antitumor screening program of the National Cancer Institute (NCI). 

The brine shrimp test (BST), the piscidal activity against Artemia salina, is related to antitumor activity and is recommended by the National Cancer Institute (NCI) as an in-house test for promising antitumor compounds [45-47], (-)-Sesamin (enantiomer of 43) and 16 showed activity against BST [48,49], Compound 16 had an ichtyotoxic effect on guppies and strongly inhibited swimming activity [50], (-P)-Tsugacetal (50) showed weak activity in the BST [51],... 

In recent years, several large targeted programs have developed. The first was in cancer chemotherapy, which was organized in 1955 when Congress asked the National Cancer Institute to undertake a large-scale attempt to find new and better antitumor drugs. 

In a blow to natural-products chemistry in the U.S., the Board of Scientific Counselors, Division of Cancer Treatment, National Cancer Institute, voted on October 2, 1981, to abolish the NCI research contract program concerned with the development of antitumor agents from plants. I fear this signals the end of significant government-sponsored research in the U.S. on medicinal plants, leaving the research to the pharmaceutical firms, who have shown relative disinterest in plant products. 

As part of their efforts to identify clinically useful antitumor compounds, the U. S. National Cancer Institute (NCI) in 1989 established a panel of 60 human tumor cell lines representing seven major categories of human cancer. They have foimd that the activity profile for various compounds is sufficiently characteristic to be employed as a means of identification, using specialized pattern-recognition algorithms. 

The first report of in vivo antitumor activity of a bryophyte appeared in 1986 in a review of results of screening of bryophytes in the National Cancer Institute s antitumor screening program by Spjut, Suffness, Cragg and Norris [20]. Subsequent studies, however, led to the conclusion that this bryophyte species, Claopodium crispifolium, was contaminated with a microorganism which contained maytansinoids, a well known class of antitumor macrolides [21]. 

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