Cisplatin resistance: Preclinical findings and clinical implications |
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Authors: | Beate Köberle Maja T TomicicSvetlana Usanova Bernd Kaina |
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Institution: | Institute of Toxicology, University Medical Center Mainz, Germany |
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Abstract: | Cisplatin is used for the treatment of many types of solid cancers. While testicular cancers respond remarkably well to cisplatin, the therapeutic efficacy of cisplatin for other solid cancers is limited because of intrinsic or acquired drug resistance. Our understanding about the mechanisms underlying cisplatin resistance has largely arisen from studies carried out with cancer cell lines in vitro. The process of cisplatin resistance appears to be multifactorial and includes changes in drug transport leading to decreased drug accumulation, increased drug detoxification, changes in DNA repair and damage bypass and/or alterations in the apoptotic cell death pathways. Translation of these preclinical findings to the clinic is emerging, but still scarce. The present review describes and discusses the clinical relevance of in vitro models by comparing the preclinical findings to data obtained in clinical studies. |
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Keywords: | Cancer Cisplatin Drug resistance DNA damage repair DNA damage bypass DNA damage response |
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