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Functional Drug Screening in the Era of Precision Medicine.

ABSTRACT: The focus of precision medicine is providing the right treatment to each unique patient. This scientific movement has incited monumental advances in oncology including the approval of effective, targeted agnostic therapies. Yet, precision oncology has focused largely on genomics in the treatment decision making process, and several recent clinical trials demonstrate that genomics is not the only variable to be considered. Drug screening in three dimensional (3D) models, including patient derived organoids, organs on a chip, xenografts, and 3D-bioprinted models provide a functional medicine perspective and necessary complement to genomic testing. In this review, we discuss the practicality of various 3D drug screening models and each model's ability to capture the patient's tumor microenvironment. We highlight the potential for enhancing precision medicine that personalized functional drug testing holds in combination with genomic testing and emerging mathematical models.

SUBMITTER: Napoli GC

PROVIDER: S-EPMC9307928 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Functional Drug Screening in the Era of Precision Medicine.

Napoli Giulia C GC Figg William D WD Chau Cindy H CH

Frontiers in medicine 20220708

The focus of precision medicine is providing the right treatment to each unique patient. This scientific movement has incited monumental advances in oncology including the approval of effective, targeted agnostic therapies. Yet, precision oncology has focused largely on genomics in the treatment decision making process, and several recent clinical trials demonstrate that genomics is not the only variable to be considered. Drug screening in three dimensional (3D) models, including patient derived ...[more]

PMID: 35879922

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Project description:Despite advances in pharmacotherapy, diabetic kidney disease (DKD) remains associated with a high burden of micro- and macrovascular complications often leading to premature mortality. New therapies are highly desirable to mitigate the burden of this disease. However, there are a number of barriers that hamper drug development in DKD. These include, amongst others, the lengthy and complex clinical trials required to prove drug efficacy and safety, inefficiencies in clinical trial conduct, and the high costs associated with these development programs. In this review a number of aspects are discussed, aiming to identify opportunities to transform and innovate drug development for DKD. Many clinical trials in DKD, as well as in other areas, face difficulties in timely and efficient enrolment of participants. To address this issue a network of sites should be created that are continuously recruiting individuals with DKD and collecting crucial information that can be used to understand prognosis and prognostic factors, and more importantly to serve as a pool of participants for recruitment to randomized trials. Second, the current clinical endpoints are late events in the progression of DKD. Endpoints based on lesser declines in estimated glomerular filtration rate (eGFR) or changes in albuminuria can shorten follow-up and/or lead to smaller and cheaper trials. Enrichment by enrolling clinical trial populations based on biomarker profiles is another approach that may facilitate clinical trial efficiency and conduct. Biomarkers can be used to individualize treatment by targeting populations more likely to respond leading to smaller and more efficient trials. Finally, using new trial design such as basket, umbrella or more broadly platform trials to assess a number of therapies simultaneously offers the potential to transform the drug development process in DKD. There are a number of opportunities to transform development approaches for new therapies for DKD. Platform trials along with appropriate biomarker-based enrichment strategies offer the possibility to foster drug development in a precision medicine era.

Dataset Information

Functional Drug Screening in the Era of Precision Medicine.

Publications

Functional Drug Screening in the Era of Precision Medicine.

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