Pharmacodynamics: biological activity of targeted therapies in clinical trials.
Clin Transl Oncol
; 9(10): 634-44, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-17974524
Anticancer drug discovery and development in cancer are currently undergoing of fast transformation. The selection of a therapeutic and effective dose using conventional cytotoxic agents has been based on the consecution of the maximally tolerated dose. However, this principle does not apply for new targeted therapies, where the definition of the optimal biologic dose (OBD) should be preferred. The definition of OBD might be established based on pharmacokinetic endpoints and, ideally, on pharmacodynamic assays by demonstrating directly the biological effect on the target and its downstream molecules in normal or tumor tissues. Normal tissues, such as peripheral blood mononuclear cells, skin or mucosa, may be excellent surrogates for explore the exposure of a drug and the dynamic target inhibition in vivo. In addition, tumor pharmacodynamic assays may determine the biologic effects of a therapy because tumor cells respond in a different way to targeted drugs than normal tissues, and to identify biomarkers that would permit to predict the individual response. In conclusion, these studies provide demonstration of proof of concept for biological and molecular mechanisms of selected drug, to select the appropriate population to be treated, to help the interpretation of clinical data, to inform the identification of optimal dose and schedule, to evaluate the clinical response and to contribute to take decisions for final approval by authorities.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ensaios de Seleção de Medicamentos Antitumorais
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Transl Oncol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Espanha
País de publicação:
Itália