An adaptive approach to therapy

An adaptive approach to therapy

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Access through your institution Buy or subscribe Analysis of a mathematical model of an evolution-based strategy for two-drug therapy has shown it could improve outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). In this study, the authors developed an evolution-based approach in which therapies are divided into primary and secondary roles, termed primary–secondary therapy. In this approach, the drug that has the highest efficacy and/or the lowest toxic effects is the primary therapy. The only role of the secondary drug is to reduce the population of cells resistant to the primary drug. Specifically, the investigators considered the context of a clinical trial of treatment of mCRPC in which the administration of abiraterone was dependent on patient response and informed by an evolution-based mathematical model. The addition of docetaxel was investigated to reduce proliferation of androgen-independent, abiraterone-resistant cells. Thus, the primary–secondary strategy in this context comprised abiraterone as the primary drug and docetaxel as the secondary therapy. Using this context, the authors quantitatively investigated the hypothesized evolutionary dynamics of this strategy using mathematical modelling. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $32.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * West, J. B. et al. Multidrug cancer therapy in metastatic castrate-resistant prostate cancer: an evolution-based strategy. _Clin. Cancer Res._ https://doi.org/10.1158/1078-0432.CCR-19-0006 (2019) Article  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Reviews Urology http://www.nature.com/nrurol/ Louise Stone Authors * Louise Stone View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Louise Stone. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Stone, L. An adaptive approach to therapy. _Nat Rev Urol_ 16, 388 (2019). https://doi.org/10.1038/s41585-019-0197-z Download citation * Published: 20 May 2019 * Issue Date: July 2019 * DOI: https://doi.org/10.1038/s41585-019-0197-z SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

Access through your institution Buy or subscribe Analysis of a mathematical model of an evolution-based strategy for two-drug therapy has shown it could improve outcomes in men with


metastatic castration-resistant prostate cancer (mCRPC). In this study, the authors developed an evolution-based approach in which therapies are divided into primary and secondary roles,


termed primary–secondary therapy. In this approach, the drug that has the highest efficacy and/or the lowest toxic effects is the primary therapy. The only role of the secondary drug is to


reduce the population of cells resistant to the primary drug. Specifically, the investigators considered the context of a clinical trial of treatment of mCRPC in which the administration of


abiraterone was dependent on patient response and informed by an evolution-based mathematical model. The addition of docetaxel was investigated to reduce proliferation of


androgen-independent, abiraterone-resistant cells. Thus, the primary–secondary strategy in this context comprised abiraterone as the primary drug and docetaxel as the secondary therapy.


Using this context, the authors quantitatively investigated the hypothesized evolutionary dynamics of this strategy using mathematical modelling. This is a preview of subscription content,


access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $32.99


/ 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on


SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about


institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * West, J. B. et al. Multidrug cancer therapy in metastatic castrate-resistant prostate


cancer: an evolution-based strategy. _Clin. Cancer Res._ https://doi.org/10.1158/1078-0432.CCR-19-0006 (2019) Article  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS


AND AFFILIATIONS * Nature Reviews Urology http://www.nature.com/nrurol/ Louise Stone Authors * Louise Stone View author publications You can also search for this author inPubMed Google


Scholar CORRESPONDING AUTHOR Correspondence to Louise Stone. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Stone, L. An adaptive approach to therapy.


_Nat Rev Urol_ 16, 388 (2019). https://doi.org/10.1038/s41585-019-0197-z Download citation * Published: 20 May 2019 * Issue Date: July 2019 * DOI: https://doi.org/10.1038/s41585-019-0197-z


SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to


clipboard Provided by the Springer Nature SharedIt content-sharing initiative