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Current Drug Targets

Volume 13 Issue 12
ISSN: 1389-4501
eISSN: 1873-5592

 

   All Titles

  Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
  pp.1525-1534 (10) Authors: Joo Ern Ang, Stan Kaye, Udai Banerji
 
 
      Abstract

Anti-cancer clinical drug development is currently costly and slow with a high attrition rate. There is thus an urgent and unmet need to integrate pharmacodynamic biomarkers into early phase clinical trials in the framework provided by the “pharmacologic audit trail” in order to overcome this challenge. This review discusses the rationale, advantages and disadvantages, as well as the practical considerations of various tissue-based approaches to perform pharmacodynamic studies in early phase oncology clinical trials using case histories of molecular targeting agents such as PI3K, m-TOR, HSP90, HDAC and PARP inhibitors. These approaches include the use of normal “surrogate” tissues such as peripheral blood mononuclear cells, platelet-rich plasma, plucked hair follicles, skin biopsies, plasma-based endocrine assays, proteomics, metabolomics and circulating endothelial cells. In addition, the review discusses the use of neoplastic tissues including tumor biopsies, circulating tumor DNA and tumor cells and metabolomic approaches. The utilization of these tissues and technology platforms to study biomarkers will help accelerate the development of molecularly targeted agents for the treatment of cancer.

 
  Keywords: Clinical trials, molecular targeted agents, oncology, pharmacodynamic biomarkers, PI3K, PARP inhibitors, neoplastic, genomic hybridization and microarray, pharmacological audit trail, surrogate tissues
  Affiliation: Drug Development Unit, Royal Marsden NHS Foundation Trust, Sycamore House, Downs Road, Sutton, SM2 5PT, UK.
 
  Key: New Content Free Content Open Access Plus Subscribed Content

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