Antineoplastic agents, polymeric

The taxane antineoplastic agents (paditaxel and docetaxel) act by promoting formation and stabilization of microtubules. Accumulation of these polymerized microtubules may lead to mitotic arrest and cell death from nonfunctional tubules. They are considered to be cell cycle-specific agents (acting with greatest activity on cells in Gap 2 [Gj] and mitosis [M] phases). 

It is obvious that this approach using nucleic bases can lead to antineoplastic polymers since several such systems have shown this activity (34,45,46,48). This is not totally unexpected since the nucleic base derivatives 5-fluorouracll and 6-mercaptopurlne are antineoplastic agents. The polymers of this type made to date have been either the Insoluble type or the soluble type polymeric drug systems. This approach should be especially effective if some directing group is also put into these polymers to carry them selectively into tumorous tissue. Research along this line is in progress in our laboratories and some other places as well. 

The present, brief review clearly shows that several different types of polymers can exhibit antineoplastic activity. It is not possible, at the present time, to state with certainty which polymeric system(s) will eventually prove to be the most useful in cancer therapy, but a directed polymeric antineoplastic agent would probably be the most desirable, if such a system can actually be synthesized. Some of the areas highlighted in this review will be considered further In some of the subsequent chapters of this book. 

Vinca alkaloids (vincristine, vinblastine, vinorelbine) are derived from the periwinkle plant (Vinca rosea). These agents work by binding to tubulin at a site different than colchicine or paclitaxel. They block polymerization, which prevents the formation of the mitotic spindle, and are used as antineoplastic agents. Taxanes produce a stabilization of microtubules similar to colchicine, but by a different mechanism, and also halt cells in metaphase. Paclitaxel (taxol) is the taxane used clinically. It is derived from the bark of the pacific yew. Taxol disrupts several microtubule-based functions as completely as inhibitors of polymerization, emphasizing the importance of assembly/disassembly balance in microtubule function. Recently, it has been found that paclitaxel also binds to and inhibits the function of a protein called bcl-2, an inhibitor of one or more pathways involved in mediating apoptosis. PaclitaxeTs interference with this function promotes apoptosis in addition to its microtubule-related inhibition of cell division. 

A D-glucan similar to Cellulose, C-48 consisting of a series of (1 3)-P-linked cellotriose units with occasional cello-biose or cellotriose residues. Polymeric. Minimum formula given. Cell wall polysaccharide in the unicellular alga Monodus subterraneus. Also prod, by Uchens. Antineoplastic agent. Amorph. powder. [a]o +18.4 (H2O). 

Thbulin-polymerizing chemotherapeutic agents, such as taxanes, have been shown to be one of the most effective drug classes in the treatment of ovarian cancer. The clinical success of paclitaxel has stimulated research into compounds with similar modes of activity in an effort to emulate its antineoplastic efficacy while minimizing its less desirable aspects, which include non-water solubility, difficult synthesis, and emerging resistance. 

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