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Unravelling mechanisms of cisplatin sensitivity and resistance in testicular cancer

Published online by Cambridge University Press:  30 September 2013

R. Koster ,
M.A.T.M. van Vugt ,
H. Timmer-Bosscha ,
J.A. Gietema  and
S. de Jong
R. Koster
Affiliation:
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
M.A.T.M. van Vugt
Affiliation:
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands
H. Timmer-Bosscha
Affiliation:
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands
J.A. Gietema
Affiliation:
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands
S. de Jong*
Affiliation:
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, The Netherlands
*
*Corresponding author: S. de Jong, PhD, Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. E-mail: [email protected]
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Abstract

Testicular cancer is the most frequent solid malignant tumour type in men 20–40 years of age. At the time of diagnosis up to 50% of the patients suffer from metastatic disease. In contrast to most other metastatic solid tumours, the majority of metastatic testicular cancer patients can be cured with highly effective cisplatin-based chemotherapy. This review aims to summarise the current knowledge on response to chemotherapy and the biological basis of cisplatin-induced apoptosis in testicular cancer. The frequent presence of wild-type TP53 and the low levels of p53 in complex with the p53 negative feed-back regulator MDM2 contribute to cisplatin sensitivity. Moreover, the high levels of the pluripotency regulator Oct4 and as a consequence of Oct4 expression high levels of miR-17/106b seed family and pro-apoptotic Noxa and the low levels of cytoplasmic p21 (WAF1/Cip1) appear to be causative for the exquisite sensitivity to cisplatin-based therapy of testicular cancer. However, resistance of testicular cancer to cisplatin-based therapy does occur and can be mediated through aberrant levels of the above mentioned key players. Drugs targeting these key players showed, at least pre-clinically, a sensitising effect to cisplatin treatment. Further clinical development of such treatment strategies will lead to new treatment options for platinum-resistant testicular cancers.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 15 , 2013 , e12
Copyright
Copyright © Cambridge University Press 2013 

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