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.
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Authors | R Koster, M A T M van Vugt, H Timmer-Bosscha, J A Gietema, S de Jong |
Journal | Expert reviews in molecular medicine
(Expert Rev Mol Med)
Vol. 15
Pg. e12
(Sep 30 2013)
ISSN: 1462-3994 [Electronic] England |
PMID | 24074238
(Publication Type: Journal Article, Review)
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Chemical References |
- Antineoplastic Agents
- Neoplasm Proteins
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Cisplatin
(pharmacology, therapeutic use)
- Drug Resistance, Neoplasm
- Genes, p53
(drug effects)
- Humans
- Male
- Neoplasm Proteins
(drug effects, genetics, metabolism)
- Testicular Neoplasms
(drug therapy, metabolism)
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