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Precision medicine: from pharmacogenomics to pharmacoproteomics

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ABSTRACT

Disease progression and drug response may vary significantly from patient to patient. Fortunately, the rapid development of high-throughput ‘omics’ technologies has allowed for the identification of potential biomarkers that may aid in the understanding of the heterogeneities in disease development and treatment outcomes. However, mechanistic gaps remain when the genome or the proteome are investigated independently in response to drug treatment. In this article, we discuss the current status of pharmacogenomics in precision medicine and highlight the needs for concordant analysis at the proteome and metabolome levels via the more recently-evolved fields of pharmacoproteomics, toxicoproteomics, and pharmacometabolomics. Integrated ‘omics’ investigations will be critical in piecing together targetable mechanisms of action for both drug development and monitoring of therapy in order to fully apply precision medicine to the clinic.

No MeSH data available.


Integration of ‘omics’ technologies for precision medicine. The realization of precision medicine via the discovery and development of biomarkers for disease detection, therapy, and prediction of drug response will involve the integration of technologies which analyze control and disease-relevant samples at the genomic, transcriptomic, and proteomic levels. This schematic details some examples of such technologies. NGS next-generation sequencing
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Fig1: Integration of ‘omics’ technologies for precision medicine. The realization of precision medicine via the discovery and development of biomarkers for disease detection, therapy, and prediction of drug response will involve the integration of technologies which analyze control and disease-relevant samples at the genomic, transcriptomic, and proteomic levels. This schematic details some examples of such technologies. NGS next-generation sequencing

Mentions: It is clear that research findings from the ‘omics’ fields of study, i.e. pharmacogenomics, transcriptomics, pharmacoproteomics, and associated areas of toxicoproteomics and pharmacometabolomics, should not be taken individually but instead should inform and complement one another (Fig. 1). Until recently, simultaneously-combined genomics and proteomics studies (‘proteogenomics’) had rarely been undertaken. However, advancements in systems pharmacology technologies and data management have allowed for what should be considered just the beginning of such complementing studies. One large initiative with this approach in mind is the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) [69]. The goal of the program is to identify potential cancer biomarker candidates by integrating genomic and proteomic analyses. In the “targeting genome to proteome” approach, cancer-related genome alterations first identified by genomic studies are then targeted at the protein level by proteomic measurements. In the “mapping proteome to genome” approach, broad-scale genomic and proteomic measurements are conducted simultaneously and then integrated. To date, this initiative has allowed for the unprecedented identification of protein pathways associated with genomically-annotated breast cancer samples [70] and our study on ovarian cancer samples [71]. These studies have identified novel therapeutic targets by linking genotype to phenotype, and ideally, further studies may compare the same genome and/or proteome data before and after treatment with new therapies geared toward these targets. CPTAC centers, including ours, are actively developing assays to detect and correlate candidate biomarkers. The resulting databases, as well as assay details, are posted to a free online repository in order to foster collaboration and standardization. Furthermore, in July 2016, NCI announced the launch of the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Network, a tri-agency coalition involving CPTAC, the Department of Veterans Affairs, and the Department of Defense. Through APOLLO, cancer patients will be screened for both genomic and proteomic abnormalities in order to match the patients to personalized, targeted therapies. Initially, the program will focus on a cohort of 8000 patients to investigate the genomics- and proteomics-based individualization of lung cancer treatment.Fig. 1


Precision medicine: from pharmacogenomics to pharmacoproteomics
Integration of ‘omics’ technologies for precision medicine. The realization of precision medicine via the discovery and development of biomarkers for disease detection, therapy, and prediction of drug response will involve the integration of technologies which analyze control and disease-relevant samples at the genomic, transcriptomic, and proteomic levels. This schematic details some examples of such technologies. NGS next-generation sequencing
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037608&req=5

Fig1: Integration of ‘omics’ technologies for precision medicine. The realization of precision medicine via the discovery and development of biomarkers for disease detection, therapy, and prediction of drug response will involve the integration of technologies which analyze control and disease-relevant samples at the genomic, transcriptomic, and proteomic levels. This schematic details some examples of such technologies. NGS next-generation sequencing
Mentions: It is clear that research findings from the ‘omics’ fields of study, i.e. pharmacogenomics, transcriptomics, pharmacoproteomics, and associated areas of toxicoproteomics and pharmacometabolomics, should not be taken individually but instead should inform and complement one another (Fig. 1). Until recently, simultaneously-combined genomics and proteomics studies (‘proteogenomics’) had rarely been undertaken. However, advancements in systems pharmacology technologies and data management have allowed for what should be considered just the beginning of such complementing studies. One large initiative with this approach in mind is the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) [69]. The goal of the program is to identify potential cancer biomarker candidates by integrating genomic and proteomic analyses. In the “targeting genome to proteome” approach, cancer-related genome alterations first identified by genomic studies are then targeted at the protein level by proteomic measurements. In the “mapping proteome to genome” approach, broad-scale genomic and proteomic measurements are conducted simultaneously and then integrated. To date, this initiative has allowed for the unprecedented identification of protein pathways associated with genomically-annotated breast cancer samples [70] and our study on ovarian cancer samples [71]. These studies have identified novel therapeutic targets by linking genotype to phenotype, and ideally, further studies may compare the same genome and/or proteome data before and after treatment with new therapies geared toward these targets. CPTAC centers, including ours, are actively developing assays to detect and correlate candidate biomarkers. The resulting databases, as well as assay details, are posted to a free online repository in order to foster collaboration and standardization. Furthermore, in July 2016, NCI announced the launch of the Applied Proteogenomics OrganizationaL Learning and Outcomes (APOLLO) Network, a tri-agency coalition involving CPTAC, the Department of Veterans Affairs, and the Department of Defense. Through APOLLO, cancer patients will be screened for both genomic and proteomic abnormalities in order to match the patients to personalized, targeted therapies. Initially, the program will focus on a cohort of 8000 patients to investigate the genomics- and proteomics-based individualization of lung cancer treatment.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Disease progression and drug response may vary significantly from patient to patient. Fortunately, the rapid development of high-throughput ‘omics’ technologies has allowed for the identification of potential biomarkers that may aid in the understanding of the heterogeneities in disease development and treatment outcomes. However, mechanistic gaps remain when the genome or the proteome are investigated independently in response to drug treatment. In this article, we discuss the current status of pharmacogenomics in precision medicine and highlight the needs for concordant analysis at the proteome and metabolome levels via the more recently-evolved fields of pharmacoproteomics, toxicoproteomics, and pharmacometabolomics. Integrated ‘omics’ investigations will be critical in piecing together targetable mechanisms of action for both drug development and monitoring of therapy in order to fully apply precision medicine to the clinic.

No MeSH data available.