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World Journal of Surgery

, Volume 24, Issue 10, pp 1183–1186 | Cite as

Molecular Analysis of Mechanisms Regulating Drug Sensitivity and the Development of New Chemotherapy Strategies for Genitourinary Carcinomas

  • Seiji  Naito
  • Hirofumi  Koga
  • Akira  Yokomizo
  • Naotaka  Sakamoto
  • Shuji  Kotoh
  • Michitaka  Nakashima
  • Akira  Kiue
  • Michihiko  Kuwano
Article

Abstract

The emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

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Copyright information

© by Société Internationale de Chirurgie 2000

Authors and Affiliations

  • Seiji  Naito
    • 1
  • Hirofumi  Koga
    • 1
  • Akira  Yokomizo
    • 1
  • Naotaka  Sakamoto
    • 1
  • Shuji  Kotoh
    • 1
  • Michitaka  Nakashima
    • 1
  • Akira  Kiue
    • 2
  • Michihiko  Kuwano
    • 3
  1. 1.Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanJP
  2. 2.Omiya Research Laboratory, Nikken Chemicals Co., 1-346 Kitabukuro, Omiya 330-0835, JapanJP
  3. 3.Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanJP

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