Clinically Relevant Resistance in Cancer Chemotherapy by Alison J. Davis, Ian F. Tannock (auth.), Borje Andersson

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By Alison J. Davis, Ian F. Tannock (auth.), Borje Andersson M.D., Ph.D, David Murray Ph.D (eds.)

Over the final a number of a long time, the advent of recent chemotherapeutic medicinal drugs and drug combos has led to elevated lengthy­ time period remission charges in different vital tumor forms. those comprise adolescence leukemia, grownup leukemias and lymphomas, in addition to testicular and trophoblastic tumors. The addition of high-dose chemotherapy with progress issue and hemopoietic stem mobile help has elevated medical remission charges even extra. for almost all of sufferers with a few of the extra universal malignancies, in spite of the fact that, palliation (rather than healing) remains to be the main real looking objective of chemotherapy for metastatic illness. The failure of chemotherapy to therapy metastatic melanoma is usually pointed out between clinicians as "drug resistance". This phenomenon can, despite the fact that, frequently be seen because the survival of malignant cells that resulted from a failure to bring an efficient drug dose to the (cellular) aim as a result of somebody of or mixture of a large number of person components. Clinically, this remedy failure is frequently seen because the swift prevalence of resistance on the unmarried telephone point. even though, in experimental structures, strong drug resistance is generally particularly gradual to emerge.

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7. 8. 9. 10. II. 12. 13. 14. 15. 16. 17. 18. 19. 20. 2\' 22. Clinically Relevant Resistance in Cancer Chemotherapy Teicher BA, Herman TS, Holden SA, et al. Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo. Science, 247 : 1457-1461, 1990. Kerbel RS, Rak J, Kobayashi H, et al. Multicellular resistance: a new paradigm to explain aspects of acquired drug resistance of solid tumors. Cold Spring Harb Symp Quant Bioi, 59:661-672, 1994. Castiglione-Gertsch M, Tattersall M, Hacking A, et al.

Repopulation of surviving cells between courses of chemotherapy seems to have been particularly neglected in the scientific and clinical literature, especially as the parallel process during radiation therapy has been characterized extensively. It is likely to be even more important after chemotherapy, where treatments are of necessity given at less frequent intervals to allow normal tissue recovery. If repopulation accelerates during continued treatment, as is seen during radiation therapy and in the few experimental studies that have addressed it following drug treatment, then this process can account for the shrinkage and regrowth of human tumors without development of any intrinsic resistance of the tumor cells.

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