• Udai Banerji and Paul Workman.
• Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London, UK.
• Semin. Oncol. 2016 Aug 1; 43 (4): 436-45.

AbstractThe 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.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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