Linked Life Data

17161682

Source:http://linkedlifedata.com/resource/pubmed/id/17161682

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-12-12
pubmed:abstractText
Rational and efficient development of new molecular cancer therapeutics requires discovery, validation, and implementation of informative biomarkers. Measurement of molecular target status, pharmacokinetic (PK) parameters of drug exposure, and pharmacodynamic (PD) endpoints of drug effects on target, pathway, and downstream biological processes are extremely important. These can be linked to therapeutic effects in what we term a "pharmacological audit trail." Using biomarkers in preclinical drug discovery and development facilitates optimization of PK, PD, and therapeutic properties so that the best agent is selected for clinical evaluation. Applying biomarkers in early clinical trials helps identify the most appropriate patients; provides proof of concept for target modulation; helps test the underlying hypothesis; informs the rational selection of dose and schedule; aids decision making, including key go/no go questions; and may explain or predict clinical outcomes. Despite many successes such as trastuzumab and imatinib, exemplifying the value of targeting specific cancer defects, only 5% of oncology drugs that enter the clinic make it to marketing approval. Use of biomarkers should reduce this high level of attrition and bring forward key decisions (e.g., "fail fast"), thereby reducing the spiraling costs of drug development and increasing the likelihood of getting innovative and active drugs to cancer patients. In this chapter, we focus primarily on PD endpoints that demonstrate target modulation, including both invasive molecular assays and functional imaging technology. We also discuss related clinical trial design issues. Implementation of biomarkers in trials remains disappointingly low and we emphasize the need for greater cooperation between various stakeholders to improve this.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-230X
pubmed:author
pubmed:issnType
Print
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
213-68
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Pharmacodynamic biomarkers for molecular cancer therapeutics.
pubmed:affiliation
Signal Transduction and Molecular Pharmacology Team, Cancer Research UK, Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, United Kingdom.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't