Multidrug resistance gene/P-glycoprotein
Much research effort has focused on developing drugs that inhibit the action of the multidrug resistance gene, abbreviated as MDR-1. This gene codes for the synthesis of p-glycoprotein, which transports chemotherapeutic drugs and other toxins out of the cell. When a cell is exposed to a stress such as the presence of chemotherapeutic drugs, the MDR-1 gene is stimulated to produce more p-glycoprotein. The result is that anticancer drugs cannot accumulate in the cell to high enough concentrations to kill the cell. Another proposed mechanism is that p-glycoprotein may change the cellular environment in such a way that the anticancer drugs cannot reach the nucleus to exert its effect. Several drugs that inhibit the action of p-glycoprotein are now undergoing clinical trials. It should be kept in mind that these drugs do not treat cancer by themselves, but to allow for the more effective use of other anticancer drugs. Valspodar, MS-209, and LY335979 are examples of synthetic compounds that are now being tested in clinical trials. Researchers are also looking to plant products for anticancer activity. Bioflavonoids are natural pigments that are common components of fruits and vegetables. There have been many health benefits attributed to the consumption of bioflavonoids. Now, researchers are discovering the mechanisms by which they may exert their effects. 3 Cinchonine is a compound similar in composition to quinine, a plant product that has been used in the treatment of malaria. This compound is effective in reversing the resistance to a chemotherapy regimen in lymphoma patients. Many compounds that act like progestogen demonstrate reversal of multidrug resistance, but their clinical application is limited due to their toxicity. Jie Li and associates 2described their study of a new non-toxic progestogen known as nomegesterol. Their results showed that the compound can indeed increase the sensitivity to the anticancer drug adriamycin.
Taxanes
Taxanes are a class of antitumor compounds with a novel mechanism of action. For tumors to grow, cell division must take place. Cell division is dependent on properly functioning microtubules in the nucleus, and taxanes interfere with this functioning. Paclitaxel was the first drug in this class, extracted from the bark of the Pacific yew. In order to avoid depletion of this rare tree, intense effort took place in laboratories to synthesize an analog that would be similar in structure, but still as active as paclitaxel. This was achieved with the synthesis of docetaxel. The two compounds have somewhat different clinical applications. 8
