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Curing metastatic cancer: lessons from testicular germ-cell tumours

Nature Reviews Cancer volume 3, pages 517–525 (2003)Cite this article

Key Points

  • Metastatic testicular germ-cell tumours (TGCTs), in contrast to nearly all other cancers in adults, can be cured with drugs (cisplatin-based combination chemotherapy). But why are metastatic TGCTs so curable?

  • TGCT cells grown in the laboratory are 2–4 times more sensitive to cisplatin than most other types of cancer cell, so they provide a representative model system with which to study the mechanisms that control cisplatin sensitivity.

  • Testis tumour cells are deficient in one particular type of DNA repair — nucleotide excision repair — and consequently have a reduced capacity to repair the DNA damage caused by cisplatin.

  • Testis tumour cells are also defective in other aspects of DNA repair and are primed for apoptosis.

  • Targeting DNA-repair proteins might sensitize other types of cancer to cisplatin.

Abstract

Most metastatic cancers are fatal. More than 80% of patients with metastatic testicular germ-cell tumours (TGCTs), however, can be cured using cisplatin-based combination chemotherapy. Why are TGCTs more sensitive to chemotherapeutics than most other tumour types? Answers to this question could lead to new treatments for metastatic cancers.

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Figure 1: Theoretical histogenesis of testicular germ-cell tumours.

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Author information

Authors and Affiliations

  1. The Prostate Cancer Research Centre, Institute of Urology, University College London, 3rd Floor, 67 Riding House Street, London, W1W 7EJ, UK

    John R.W. Masters

  2. University of Pittsburgh Cancer Institute, Hillman Cancer Center, Research Pavilion Suite 263/2.1, 5117 Center Avenue, Pittsburgh, 15213-1863, Pennsylvania, USA

    Beate Köberle

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DATABASES

Cancer.gov

bladder cancer

breast cancer

colon cancer

ovarian cancer

small-cell lung cancer

stomach cancer

testicular cancer

LocusLink

AP endonuclease

ATase

BAX

BCL2

BCL-XL

caspase-9

ERCC1

HR23B

HSP27

MDM2

p53

PCNA

RFC

RPA

Trp53

XPA

XPB

XPC

XPD

XPF

XPG

XRCC1

OMIM

xeroderma pigmentosum

FURTHER INFORMATION

Cancer UK

Human DNA repair genes

National Cancer Institute

Glossary

THIOLS

Compounds that contain -SH as the principal group directly attached to carbon, such as glutathione. Glutathione is the main endogenous antioxidant produced by the cell. It participates in the neutralization of free radicals, reactive oxygen compounds, and maintains exogenous antioxidants such as vitamins C and E in their reduced (active) forms. In addition, through direct conjugation by glutathione-S-transferase, glutathione detoxifies many compounds.

CLONOGENIC ASSAY

Measures the proportion of single cells that are able to form colonies (minimum of 32 cells). It is used to estimate survival and dose response to drug treatment.

ATOMIC ABSORPTION SPECTROSCOPY

This technique uses light absorption to measure the concentration of atoms in gas phase (usually following vaporization of a solid or liquid in a furnace).

ALKALINE ELUTION

This technique measures the rate of DNA elution through a filter membrane under alkaline conditions. The amount of DNA single-strand breaks (or other lesions converted to single-strand breaks) is estimated on the basis of the increase in the rate of DNA elution.

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Masters, J., Köberle, B. Curing metastatic cancer: lessons from testicular germ-cell tumours. Nat Rev Cancer 3, 517–525 (2003). https://doi.org/10.1038/nrc1120

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