LETTER DRUG DISCOVERY
Author Response to Comment on “Drug Discovery: Turning the Titanic” Elias A. Zerhouni In the face of poorly understood disease complexity, a diversity of approaches is the best strategy.
Sanofi, 75008 Paris, France. E-mail: [email protected]
In degenerative diseases, on the other hand, once the structural damage is done, it appears unlikely that resolution studies would be likely to succeed. Alzheimer’s disease is an example in which the field is now convinced that early intervention driven by early diagnosis will be the key to successful clinical outcomes (3). In brief, we may be talking about two faces of the same coin, and both research avenues—provided that they are applied to human disease biology and disease models—may well be necessary as proposed by the authors. In the face of poorly understood complexity, a diversity of approaches is the best strategy.
REFERENCES 1. E. A. Zerhouni, Turning the Titanic. Sci. Transl. Med. 6, 221ed2 (2014). 2. W. J. Lesterhuis, A. Bosco, R. A. Lake, Comment on “Drug discovery: Turning the Titanic.” Sci. Transl. Med. 6, 229le2 (2014). 3. R. A. Sperling, C. R. Jack, P. S. Aisen, Testing the right target and right drug at the right stage. Sci. Transl. Med. 3, 111cm33 (2011). Submitted 18 February 2014 Accepted 24 February 2014 Published 26 March 2014 10.1126/scitranslmed.3008817 Citation: E. A. Zerhouni, Author response to comment on “Drug discovery: Turning the Titanic.” Sci. Transl. Med. 6, 229lr2 (2014).
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Regarding my recent Editorial (1), I thank Lesterhuis et al. (2) for their Letter, which provides an interesting perspective to the classical approaches to understanding human disease pathobiology. To study disease resolution pathways as posited by then authors is certainly appropriate, because no one knows if forward pathological causal pathways are the same as backward pathological resolution pathways. We lack fundamental knowledge on whether biology, once disturbed, will return to normalcy by simply reversing what caused the disease in the first place. In the specific case of cancer biology, our lack of understanding regarding resolution mechanisms and physiological pathways is especially profound. Efforts are already under way to study tumor responses and mechanisms of resistance by repeated sampling of tumor tissue and using emerging methods of assessing circulating tumor DNA, RNA, and other biomarkers during therapy. From my perspective, the approach offered by the authors is certainly complementary to the classical approach and should be tested further not only in oncology but also, when possible, in all chronic diseases. There are instances in which an understanding of the factors that lead to remission in chronic relapsing diseases, such as in autoimmune disorders (for example, multiple sclerosis), could provide insights that predisease biological studies may not.
Author Response to Comment on ''Drug Discovery: Turning the Titanic'' Elias A. Zerhouni (March 26, 2014) Science Translational Medicine 6 (229), 229lr2. [doi: 10.1126/scitranslmed.3008817] Editor's Summary
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Science Translational Medicine (print ISSN 1946-6234; online ISSN 1946-6242) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science Translational Medicine is a registered trademark of AAAS.
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Author Response to Comment on “Drug Discovery: Turning the Titanic” Elias A. Zerhouni In the face of poorly understood disease complexity, a diversity of approaches is the best strategy.
Sanofi, 75008 Paris, France. E-mail: [email protected]
In degenerative diseases, on the other hand, once the structural damage is done, it appears unlikely that resolution studies would be likely to succeed. Alzheimer’s disease is an example in which the field is now convinced that early intervention driven by early diagnosis will be the key to successful clinical outcomes (3). In brief, we may be talking about two faces of the same coin, and both research avenues—provided that they are applied to human disease biology and disease models—may well be necessary as proposed by the authors. In the face of poorly understood complexity, a diversity of approaches is the best strategy.
REFERENCES 1. E. A. Zerhouni, Turning the Titanic. Sci. Transl. Med. 6, 221ed2 (2014). 2. W. J. Lesterhuis, A. Bosco, R. A. Lake, Comment on “Drug discovery: Turning the Titanic.” Sci. Transl. Med. 6, 229le2 (2014). 3. R. A. Sperling, C. R. Jack, P. S. Aisen, Testing the right target and right drug at the right stage. Sci. Transl. Med. 3, 111cm33 (2011). Submitted 18 February 2014 Accepted 24 February 2014 Published 26 March 2014 10.1126/scitranslmed.3008817 Citation: E. A. Zerhouni, Author response to comment on “Drug discovery: Turning the Titanic.” Sci. Transl. Med. 6, 229lr2 (2014).
www.ScienceTranslationalMedicine.org
26 March 2014
Vol 6 Issue 229 229lr2
1
Downloaded from http://stm.sciencemag.org/ on November 15, 2015
Regarding my recent Editorial (1), I thank Lesterhuis et al. (2) for their Letter, which provides an interesting perspective to the classical approaches to understanding human disease pathobiology. To study disease resolution pathways as posited by then authors is certainly appropriate, because no one knows if forward pathological causal pathways are the same as backward pathological resolution pathways. We lack fundamental knowledge on whether biology, once disturbed, will return to normalcy by simply reversing what caused the disease in the first place. In the specific case of cancer biology, our lack of understanding regarding resolution mechanisms and physiological pathways is especially profound. Efforts are already under way to study tumor responses and mechanisms of resistance by repeated sampling of tumor tissue and using emerging methods of assessing circulating tumor DNA, RNA, and other biomarkers during therapy. From my perspective, the approach offered by the authors is certainly complementary to the classical approach and should be tested further not only in oncology but also, when possible, in all chronic diseases. There are instances in which an understanding of the factors that lead to remission in chronic relapsing diseases, such as in autoimmune disorders (for example, multiple sclerosis), could provide insights that predisease biological studies may not.
Author Response to Comment on ''Drug Discovery: Turning the Titanic'' Elias A. Zerhouni (March 26, 2014) Science Translational Medicine 6 (229), 229lr2. [doi: 10.1126/scitranslmed.3008817] Editor's Summary
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Visit the online version of this article to access the personalization and article tools: http://stm.sciencemag.org/content/6/229/229lr2 Obtain information about reproducing this article: http://www.sciencemag.org/about/permissions.dtl
Science Translational Medicine (print ISSN 1946-6234; online ISSN 1946-6242) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science Translational Medicine is a registered trademark of AAAS.
Downloaded from http://stm.sciencemag.org/ on November 15, 2015
The following resources related to this article are available online at http://stm.sciencemag.org. This information is current as of November 15, 2015.
