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Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses

Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an “atypical response” will increase understanding of the mechanisms involved in cance...

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Detalles Bibliográficos
Autores principales: De La Torre, Kristine, Cohen, Elly, Loeser, Anne, Hurlbert, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460258/
https://www.ncbi.nlm.nih.gov/pubmed/28649647
http://dx.doi.org/10.1038/s41523-017-0010-1
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author De La Torre, Kristine
Cohen, Elly
Loeser, Anne
Hurlbert, Marc
author_facet De La Torre, Kristine
Cohen, Elly
Loeser, Anne
Hurlbert, Marc
author_sort De La Torre, Kristine
collection PubMed
description Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an “atypical response” will increase understanding of the mechanisms involved in cancer progression and treatment resistance, accelerate biomarker identification, and improve precision medicine by allowing clinicians to prospectively select optimal treatments. Based on our review, we suggest two ways to move this field forward. First, we suggest that clear categorization of “atypical responders” is needed. This encompasses three sub-categories of patients: “exceptional responders” (those with an unusually favorable treatment response), “rapid progressors” (patients demonstrating an unusually poor or no therapeutic response), and “exceptional survivors” (patients who have far outlived their initial prognosis). Such categorization may depend upon the clinical context and disease subtype. Second, we suggest that atypical responses may be due not only to somatic mutations in tumors, but also to inherited polymorphisms in non-tumor tissue, host and tumor environments, lifestyle factors, co-morbidities, use of complementary and integrative medicine, and the interaction among these components. Here, we summarize new research initiatives exploring atypical responses, the potential reasons for atypical responses, and a strategic call to action. Rigorous studies of normal and atypical responses to treatment will be needed to strengthen understanding of the role of non-tumor factors. Clinical trial design for targeted and other types of therapies should be enhanced to collect data in a standardized manner beyond tumor genetics, resulting in more thorough study of the whole patient.
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spelling pubmed-54602582017-06-23 Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses De La Torre, Kristine Cohen, Elly Loeser, Anne Hurlbert, Marc NPJ Breast Cancer Perspective Clinical research generally focuses on results involving a statistical mean with little attention in trial design to patients who respond considerably better or worse than average. Exploring the reasons underlying an “atypical response” will increase understanding of the mechanisms involved in cancer progression and treatment resistance, accelerate biomarker identification, and improve precision medicine by allowing clinicians to prospectively select optimal treatments. Based on our review, we suggest two ways to move this field forward. First, we suggest that clear categorization of “atypical responders” is needed. This encompasses three sub-categories of patients: “exceptional responders” (those with an unusually favorable treatment response), “rapid progressors” (patients demonstrating an unusually poor or no therapeutic response), and “exceptional survivors” (patients who have far outlived their initial prognosis). Such categorization may depend upon the clinical context and disease subtype. Second, we suggest that atypical responses may be due not only to somatic mutations in tumors, but also to inherited polymorphisms in non-tumor tissue, host and tumor environments, lifestyle factors, co-morbidities, use of complementary and integrative medicine, and the interaction among these components. Here, we summarize new research initiatives exploring atypical responses, the potential reasons for atypical responses, and a strategic call to action. Rigorous studies of normal and atypical responses to treatment will be needed to strengthen understanding of the role of non-tumor factors. Clinical trial design for targeted and other types of therapies should be enhanced to collect data in a standardized manner beyond tumor genetics, resulting in more thorough study of the whole patient. Nature Publishing Group UK 2017-03-16 /pmc/articles/PMC5460258/ /pubmed/28649647 http://dx.doi.org/10.1038/s41523-017-0010-1 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Perspective
De La Torre, Kristine
Cohen, Elly
Loeser, Anne
Hurlbert, Marc
Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title_full Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title_fullStr Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title_full_unstemmed Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title_short Moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
title_sort moonshots and metastatic disease: the need for a multi-faceted approach when studying atypical responses
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460258/
https://www.ncbi.nlm.nih.gov/pubmed/28649647
http://dx.doi.org/10.1038/s41523-017-0010-1
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