Antineoplastic agent clinical development

To function, Ras must be attached to the plasma membrane. Translocation from the cytoplasm to membrane requires a series of posttranslational modifications that begin with farnesylation of the cysteine residue, the fourth amino acid residue from the C terminus of the protein, by famesyl protein transferase (FPTase) (64). Attachment of the hydrophobic 15-carbon lipid farnesyl group allows Ras molecule insertion into the plasma membrane and is crucial for Ras signaling activity and transformation properties. As farnesylation is required for oncogenic Ras function, FPTase inhibitors (FTIs) are obvious candidate antineoplastic agents. Several drugs that inhibit Ras farnesylation are at various stages of clinical development (65). 

Many other alkaloid-based medicines exist. Drugs based on berberine are used in the treatment of infections as well as in the treatment of AIDS. The taxanes (e.g., paclitaxel in Taxol drug and its synthetic analogue, docetaxel in Taxotere) have antineoplastic agents to cure cancers, Kaposi s sarcoma, and squamous cell carcinomas. Several novel alkaloids and their synthetic analogues are under development and considered to being accepted by U.S. Food and Drug Administration for clinical use. ... 

The advent of gene-splicing technology and other developments and improvements in molecular biology techniques have allowed for commercial production of these and other cytokines discussed here, in quantities adequate for clinical evaluation, as well as for those deemed successful for therapeutical applications as (see Table 15-1). Agents now available have significant antiviral activity. Antineoplastic utility has been demonstrated more... 

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