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Clinical trial design in the era of precision medicine

Recent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for sev...

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Autores principales: Fountzilas, Elena, Tsimberidou, Apostolia M., Vo, Henry Hiep, Kurzrock, Razelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428375/
https://www.ncbi.nlm.nih.gov/pubmed/36045401
http://dx.doi.org/10.1186/s13073-022-01102-1
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author Fountzilas, Elena
Tsimberidou, Apostolia M.
Vo, Henry Hiep
Kurzrock, Razelle
author_facet Fountzilas, Elena
Tsimberidou, Apostolia M.
Vo, Henry Hiep
Kurzrock, Razelle
author_sort Fountzilas, Elena
collection PubMed
description Recent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant standard phase I, II, and III protocols, allowing for accelerated drug evaluation and approval and molecular-based individualized treatment. Furthermore, real-world data, as well as exploitation of digital apps and structured observational registries, and the utilization of machine learning and/or artificial intelligence, may further accelerate knowledge acquisition. Overall, clinical trials have evolved, shifting from tumor type-centered to gene-directed and histology-agnostic trials, with innovative adaptive designs and personalized combination treatment strategies tailored to individual biomarker profiles. Some, but not all, novel trials now demonstrate that matched therapy correlates with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To further improve the precision medicine paradigm, the strategy of matching drugs to patients based on molecular features should be implemented earlier in the disease course, and cancers should have comprehensive multi-omic (genomics, transcriptomics, proteomics, immunomic) tumor profiling. To overcome cancer complexity, moving from drug-centric to patient-centric individualized combination therapy is critical. This review focuses on the design, advantages, limitations, and challenges of a spectrum of clinical trial designs in the era of precision oncology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-022-01102-1.
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spelling pubmed-94283752022-08-31 Clinical trial design in the era of precision medicine Fountzilas, Elena Tsimberidou, Apostolia M. Vo, Henry Hiep Kurzrock, Razelle Genome Med Review Recent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant standard phase I, II, and III protocols, allowing for accelerated drug evaluation and approval and molecular-based individualized treatment. Furthermore, real-world data, as well as exploitation of digital apps and structured observational registries, and the utilization of machine learning and/or artificial intelligence, may further accelerate knowledge acquisition. Overall, clinical trials have evolved, shifting from tumor type-centered to gene-directed and histology-agnostic trials, with innovative adaptive designs and personalized combination treatment strategies tailored to individual biomarker profiles. Some, but not all, novel trials now demonstrate that matched therapy correlates with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To further improve the precision medicine paradigm, the strategy of matching drugs to patients based on molecular features should be implemented earlier in the disease course, and cancers should have comprehensive multi-omic (genomics, transcriptomics, proteomics, immunomic) tumor profiling. To overcome cancer complexity, moving from drug-centric to patient-centric individualized combination therapy is critical. This review focuses on the design, advantages, limitations, and challenges of a spectrum of clinical trial designs in the era of precision oncology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13073-022-01102-1. BioMed Central 2022-08-31 /pmc/articles/PMC9428375/ /pubmed/36045401 http://dx.doi.org/10.1186/s13073-022-01102-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Fountzilas, Elena
Tsimberidou, Apostolia M.
Vo, Henry Hiep
Kurzrock, Razelle
Clinical trial design in the era of precision medicine
title Clinical trial design in the era of precision medicine
title_full Clinical trial design in the era of precision medicine
title_fullStr Clinical trial design in the era of precision medicine
title_full_unstemmed Clinical trial design in the era of precision medicine
title_short Clinical trial design in the era of precision medicine
title_sort clinical trial design in the era of precision medicine
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428375/
https://www.ncbi.nlm.nih.gov/pubmed/36045401
http://dx.doi.org/10.1186/s13073-022-01102-1
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