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Preclinical cancer-target validation: How not to be wrong

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Air date: Wednesday, January 24, 2018, 3:00:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 1210, (292 Live, 918 On-demand)
Category: WALS - Wednesday Afternoon Lectures
Runtime: 01:05:27
Description: Wednesday Afternoon Lecture Series

Published and unpublished studies by investigators in the pharmaceutical industry indicate that a disturbingly high number of academic laboratories' reports nominating potential new cancer-drug targets are either non-reproducible or, if reproducible, are not sufficiently robust to form the basis for drug-discovery efforts. The reasons are likely multifactorial, including the ubiquitous use of "down" assays in cancer biology (e.g. decreased cell proliferation, decreased tumor growth, etc.) that incorporate chemical and genetic perturbants that are prone to cause off-target effects, failure to adequately correct for multiple hypothesis testing, flawed logic when inferring causality from correlative data, and publication bias in favor of "positive" results. Improving the veracity and robustness of preclinical target-validation studies will require setting higher standards in terms of the logic, controls, and corroboration underlying their conclusions. These standards will hopefully discourage the now common practice of relegating target identification and validation experiments to the last figures of papers in an (often gratuitous) attempt to justify their "clinically relevance." Real translation happens when one has finally gathered enough knowledge to know what can be done, not by coercing basic scientists to be translational scientists.

For more information go to https://oir.nih.gov/wals/2017-2018/preclinical-cancer-target-validation-how-not-be-wrong
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NLM Title: Preclinical cancer-target validation : how not to be wrong / William G. Kaelin, Jr.
Author: Kaelin, William G.
National Institutes of Health (U.S.),
Publisher:
Abstract: (CIT): Wednesday Afternoon Lecture Series Published and unpublished studies by investigators in the pharmaceutical industry indicate that a disturbingly high number of academic laboratories' reports nominating potential new cancer-drug targets are either non-reproducible or, if reproducible, are not sufficiently robust to form the basis for drug-discovery efforts. The reasons are likely multifactorial, including the ubiquitous use of "down" assays in cancer biology (e.g. decreased cell proliferation, decreased tumor growth, etc.) that incorporate chemical and genetic perturbants that are prone to cause off-target effects, failure to adequately correct for multiple hypothesis testing, flawed logic when inferring causality from correlative data, and publication bias in favor of "positive" results. Improving the veracity and robustness of preclinical target-validation studies will require setting higher standards in terms of the logic, controls, and corroboration underlying their conclusions. These standards will hopefully discourage the now common practice of relegating target identification and validation experiments to the last figures of papers in an (often gratuitous) attempt to justify their "clinically relevance." Real translation happens when one has finally gathered enough knowledge to know what can be done, not by coercing basic scientists to be translational scientists.
Subjects: Antineoplastic Agents
Drug Delivery Systems
Drug Evaluation, Preclinical
Validation Studies as Topic
Publication Types: Lecture
Webcasts
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NLM Classification: QV 269
NLM ID: 101720653
CIT Live ID: 27066
Permanent link: https://videocast.nih.gov/launch.asp?23671