Скачать или смотреть Preclinical cancer-target validation: How not to be wrong

Preclinical cancer-target validation: How not to be wrong

Air date: Wednesday, January 24, 2018, 3:00:00 PM

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Published and unpublished studies by investigators in the pharmaceutical industry indicate that a disturbingly high number of academic laboratories' reports nominating potential new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/pr...

Author: William G. Kaelin Jr., M.D., Senior Physician, Brigham and Women's Hospital; Co-Leader, Dana-Farber Cancer Institute/Harvard Cancer Center Program in Kidney Cancer; Professor, Harvard Medical School; Investigator, Howard Hughes Medical Institute

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