Cancer chemotherapy strategies

Epothilones A, B and E (4,5 and 6) (Fig. 2) are representative members of a new class of bacterially derived natural products which exhibit potent biological activity. Isolated by Hofle and coworkers [6] from a soil sample collected near the Zambesi river, the compounds have provided a great deal of excitement in the scientific community due to their potent cytotoxicity against a number of multiple drug-resistant tumor cell lines and because of the mechanism by which they exert this effect. Like Taxol [7], the epothilones promote the combination of a- and 3-tubulin subunits and stabilize the resulting microtubule structures. This mode of action inhibits the cell division process and is, therefore, an attractive strategy for cancer chemotherapy [7,8]. 

Carcinogenesis involves a complex series of genetic and biochemical events that enable transformed cells to proliferate, metastasize, migrate to secondary sites, and, sometimes, acquire resistance to chemotherapy. In Sect. 25.4.1, we will discuss how caveolin-1 expression correlates with cancerous growth, a potential mechanism of chemotherapy drug resistance, and how caveolae may be particularly exploited for cancer therapeutic strategies. 

Chronic gout can be caused by (1) a genetic defect, for example, one resulting in an increase in the rate of purine synthesis, (2) renal deficiency, (3) Lesch-Nyhan Syndrome,4 or (4) excessive synthesis of uric acid associated with cancer chemotherapy. Treatment strategies for chronic gout include the use of uricosuric drugs that increase the excretion of uric acid, thereby reducing its concentration in plasma, and the use of allopurinol, which is a selective inhibitor of the terminal steps in the biosynthesis of uric acid. 

That is why the best strategy of cancer chemotherapy is medical treatment at minimum tumor size before the cells will acquire resistance and ability to metastasis. Correspondingly, if the treatment was started then maximum number of effective preparations should be applied as soon as possible. The main problem at that is prevention of development of cells resistance to a lot of cytostatic agents in the case of acquiring of such ability in relation to one of them. This recommendation corresponds to principles underlying combined chemotherapy. 

Nocentini, G., 1996, Ribonucleotide reductase inhibitors new strategies for cancer chemotherapy. Crit. Rev. Oncol. Hematol. 22 899126. 

Recently, new prodrug strategies aimed at targeting a specific enzyme or a specific membrane transporter or both, facilitated by simultaneous use of gene delivery engineered to express the requisite enzyme or transporter, have been developed and proposed to be especially useful in cancer chemotherapy (90). 

Kaufman D, Chabner BA. Clinical strategies for cancer treatment The role of drugs, in Chabner BA, Longo DL, eds. Cancer Chemotherapy and Biotherapy Principles and Practice. Philadelphia, Lippincott-Raven, 1996 1-16. 

After their discovery, the Vinca alkaloids became the first natural anticancer agents to be clinically used, and they are still an indispensable part of most curative regimens used in cancer chemotherapy nowadays. On the other hand, the plant producing these alkaloids, C. roseus, has become one of the most extensively studied medicinal plants. The levels of vincristine and vinblastine in the plant revealed to be extremely low and, for pharmaceutical production, approximately half a ton of dry leaves is needed to obtain 1 g of vinblastine [4]. This feet stimulated intense investigation in alternative methods for the production of vinblastine and vincristine, namely chemical synthesis and plant cell cultures. However, chemical synthesis showed not to be viable due to the high number of transformations involved, and the anticancer alkaloids were never detected in cell cultures, which express alkaloid metabolism very poorly [5, 6]. The biosynthetic pathway of terpenoid indole alkaloids in C. roseus has also been intensively studied with the objective of developing a manipulation strategy to improve the levels of the anticancer alkaloids in the leaves of the plant [5, 7-10]. 

Recruitment strategy in cancer chemotherapy involves the initial use of a CCNS drug (eg, doxorubicin) to achieve a significant log kill. This results in the recruitment into cell division of resting... 

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