Critical parameters in targeted drug development: the pharmacological audit trail.

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Publication Date
2016-08Author
Banerji, U
Workman, P
Type
Journal Article
Metadata
Show full item recordAbstract
The Pharmacological Audit Trail (PhAT) comprises a set of critical questions that need to be asked during discovery and development of an anticancer drug. Key aspects include: (1) defining a patient population; (2) establishing pharmacokinetic characteristics; (3) providing evidence of target engagement, pathway modulation, and biological effect with proof of concept pharmacodynamic biomarkers; (4) determining intermediate biomarkers of response; (5) assessing tumor response; and (6) determining how to overcome resistance by combination or sequential therapy and new target/drug discovery. The questions asked in the PhAT should be viewed as a continuum and not used in isolation. Different drug development programmes derive different types of benefit from these questions. The PhAT is critical in making go-no-go decisions in the development of currently studied drugs and will continue to be relevant to discovery and development of future generations of anticancer agents.
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Licenseref URL
https://creativecommons.org/licenses/by-nc-nd/4.0Version of record
Subject
Humans
Neoplasms
DNA Damage
Neovascularization, Pathologic
Antineoplastic Agents
Positron-Emission Tomography
Treatment Outcome
Apoptosis
Cell Proliferation
Drug Resistance, Neoplasm
Patient Selection
Drug Discovery
Biomarkers, Tumor
Research team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Language
eng
Date accepted
2015-10-23
License start date
2016-08
Citation
Seminars in oncology, 2016, 43 (4), pp. 436 - 445