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Cancer Chemotherapy and Pharmacology

, Volume 56, Supplement 1, pp 90–93 | Cite as

Translational studies for target-based drugs

  • Kazuto NishioEmail author
  • Tokuzo Arao
  • Tatsu Shimoyama
  • Yasuhiro Fujiwara
  • Tomohide Tamura
  • Nagahiro Saijo
Article

Abstract

The biological background for the clinical and prognostic heterogeneity among tumors within the same histological subgroup is due to individual variations in the biology of tumors. The number of investigations looking at the application of novel technologies within the setting of clinical trials is increasing. The most promising way to improve cancer treatment is to build clinical research strategies on intricate biological evidence. New genomic technologies have been developed over recent years. These techniques are able to analyze thousands of genes and their expression profiles simultaneously. The purpose of this approach is to discover new cancer biomarkers, to improve diagnosis, predict clinical outcomes of disease and response to treatment, and to select new targets for novel agents with innovative mechanisms of action. Gene expression profiles are also used to assist in selecting biomarkers of pharmacodynamic effects of drugs in the clinical setting. Biomarker monitoring in surrogate tissues may allow researchers to assess “proof of principle” of new treatments. Clinical studies of biomarkers monitoring toxicity profiles have also been done. Such pharmacodynamic markers usually respond to treatment earlier than clinical response, and as such may be useful predictors of efficacy. Epidermal growth factor receptor (EGFR) mutation in lung cancer tissues is a strong predictive biomarker for EGFR-targeted protein tyrosine kinase inhibitors. Monitoring of EGFR mutation has been broadly performed in retrospective and prospective clinical studies. However, global standardization for the assay system is essential for such molecular correlative studies. A more sensitive assay for EGFR mutation is now under evaluation for small biopsy samples. Microdissection for tumor samples is also useful for the sensitive detection of EGFR mutation. Novel approaches for the detection of EGFR mutation in other clinical samples such as cytology, pleural effusion and circulating tumor cells are ongoing.

Keywords

Biomarker Proof of principle Pharmacodynamic marker EGFR mutation 

Notes

Acknowledgements

This work was supported by funds for the Third Term Comprehensive 10-Year Strategy for Cancer Control and a Grant-in-Aid for Scientific Research and for Health and Labour Science Research Grants, Research on Advanced Medical Technology, H14-Toxico-007.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Kazuto Nishio
    • 1
    • 3
    Email author
  • Tokuzo Arao
    • 1
    • 3
  • Tatsu Shimoyama
    • 1
    • 2
  • Yasuhiro Fujiwara
    • 2
  • Tomohide Tamura
    • 2
  • Nagahiro Saijo
    • 2
  1. 1.Shien LabNational Cancer Center HospitalTokyoJapan
  2. 2.Medical OncologyNational Cancer Center HospitalTokyoJapan
  3. 3.Pharmacology DivisionNational Cancer Center Research InstituteTokyoJapan

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