Cancer chemotherapy-resistant

Despite dramatic advances in the treatment of several human malignancies including Hodgkin s lymphomas and leukemias, dmg resistance remains a pressing issue in cancer chemotherapy. Acquired or induced dmg resistance afflicts practically all classes of cancer agents. It usually is manifested clinically... 

Cancer chemotherapy and the treatment of cancers are analogous to anti-infectives and the treatment of infections. Cancer cells may be sensitive to certain chemotherapy agents, but then with repeated exposure, the cells become resistant to treatment. The resistant cells then grow and multiply. While tumors may be tested for chemotherapy sensitivity, this area is still developing. Today, tumor sensitivity can demonstrate tumor resistance so that needless exposure to an inadequate therapy and its toxicity can be avoided. 

Radiation therapy is the treatment of choice for chemotherapy-resistant tumors such as non-small cell lung cancer (NSCLC) or in chemotherapy-refractory patients with SVCS. Between 70% and 90% of patients will experience relief of symptoms. Radiation therapy also may be combined with chemotherapy for chemotherapy-sensitive tumors such as SCLC and lymphoma. In the rare emergency situations of airway obstruction or elevated intracranial pressure, empirical radiotherapy prior to tissue diagnosis should be used. In most patients, symptoms resolve within 1 to 3 weeks. 

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]. 

Pronzato P. (2008) New therapeutic options for chemotherapy resistant metastatic breast cancer The epothilones. Drugs 68 139-146. 

In addition to be a direct target of antitumor treatment, PKC has been shown to be involved in the resistance to antitumor treatment and in the modulation of apoptosis. Resistance to cancer chemotherapy is a major... 

Eastman A, Schulte N, Sheibani N, Sorenson CM. Mechanisms of resistance to platinum drugs. In (Nicolini M, ed), Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 1988 Martinus Nijhoff Publishing Boston, pp. 178-196. 

Three classes of plant-derived drugs, the vinca alkaloids (vincristine, vinblastine, and vinorelbine), the epipodo-phyllotoxins (etoposide and teniposide and the tax-anes (paclitaxel and taxotere), are used in cancer chemotherapy. These classes differ in their structures and mechanisms of action but share the multidrug resistance mechanism, since they are all substrates for the multidrug transporter P-glycoprotein. 

Nausea that accompanies the administration of cancer chemotherapy agents was resistant to drug intervention until the introduction of the serotonin receptor antagonist odansetron (see Chapter 13). The benzimidazolone-based compound itasetron (57-6) has much the same activity as its tricylcic predecessor. Condensation of 2-nitrophenyl-isocyanate (57-1) with the bridged bycyclic diamine (57-2) leads to the addition... 

The clinical implications of both amplification and loss in tumors have been studied. In a study of 29 Dukes C colorectal cancer patients, those with tumors that had two or more chromosomal regions of gain or loss had significantly better prognosis than patients with less (p = 0.02) (21). Loss of chromosome 5q and lack of 8q amplification in serous ovarian cancer n = 96) is associated with improved prognosis (5-year survival of 75% versus 0% with no loss on 5q and amplification on 8q p = 0.0007) (22). In childhood ALL the amplification of specific chromosomes, chromosome regions, and genes has been associated with chemotherapy resistance and clinical outcome (23,24). 

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