Response of Testicular Tumors to Chemotherapy

Relative Role of Drug—DNA Interactions and Apoptosis
  • Christine M. Chresta
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Testicular germ cell tumors (GCT) are one of the few solid tumors that can be cured by chemotherapy, even when metastatic. The success of therapy is probably related to the unusual susceptibility of this tumor type to undergo apoptosis. The DNA damage threshold for drug-induced apoptosis is very low and the kinetics of programmed cell death are unusually rapid, being more similar to those of hematological malignancies than those of other solid tumors. This chapter
Table 1

Anticancer Agents that Have Produced Complete Responses in Testicular Germ Cell Tumors

Drug

Mechanism of action

Ref. and date

Actinomycin D ±

Transcription

(1), 1960

Methotrexate or

Antimetabolite

 

Chlorambucil

Alkylation/crosslink

 

Bleomycin

Free radical SSB and DSB

(35), 1980

Vinblastine

Microtubule (destabilizer)

 

Cisplatin ±

Platination/crosslink

(36), 1974

Bleomycin

 

(37), 1977

Vinblastine

  

Etoposide ±

Topoisomerase II poison

(38), 1980

Cisplatin

 

(39), 1987

Bleomycin

  

Taxol

Microtubule (stabilizer)

(40), 1996

Summary of some of the clinical trials that have resulted in complete responses in patients with testicular GCTs. It demonstrates that this disease is responsive to agents of many different mechanisms of action so that Taxol, cisplatin, and etoposide have all shown activity against this disease as single agents.

outlines the genetic alterations that occur during conversion of the normal germ cell into a pluripotential tumor, and discusses how they could contribute to drug sensitivity. It also analyzes the relative roles that drug—DNA interactions and apoptosis play in chemosensitivity. Recent studies employing isogenic cell line pairs of GCTs differing in expression of p53, and the Bcl-2 family members show that these proteins play an important role in both drug-induced apoptosis and long-term loss of reproductive potential in this disease.

Keywords

Germ Cell Testicular Tumor Apoptosis Susceptibility Testicular GCTs Human Germ Cell Tumour 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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© Springer Science+Business Media New York 1999

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  • Christine M. Chresta

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