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Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
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The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
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Updated: Apr 4, 2026

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
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Functional Genomics in Pharmaceutical Drug Discovery.

Robert Adams1, Michael Steckel1, Barbara Nicke2

  • 1Bayer Pharma AG, Muellerstr. 178, 13353, Berlin, Germany.

Handbook of Experimental Pharmacology
|September 3, 2015
PubMed
Summary

Personalized medicine relies on identifying molecular changes for targeted therapies. Advanced genomic technologies, including RNA interference (RNAi) and CRISPR/Cas9 screening, accelerate the discovery of new drug targets.

Keywords:
CRISPR/Cas9Functional genomicsHigh-content assayHigh-throughput screeningRNA interference (RNAi)Short hairpin RNA (shRNA)Short interfering RNA (siRNA)

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Area of Science:

  • Genomics and Molecular Biology
  • Drug Discovery and Development
  • Personalized Medicine

Background:

  • Targeted therapies in personalized medicine necessitate understanding patient-specific molecular disease drivers.
  • The 21st century has seen a surge in technologies for detecting molecular changes, crucial for initiating drug development.
  • Genomic and functional genomics methods have significantly enhanced the identification of drug targets and their disease relevance.

Purpose of the Study:

  • To review the role of functional genomics in identifying novel drug targets.
  • To discuss high-throughput RNA interference (RNAi) screening as an established method for target identification.
  • To briefly explore the potential of CRISPR/Cas9 as a functional screening tool.

Main Methods:

  • Utilizing next-generation genome sequencing to identify molecular changes.
  • Employing sophisticated genome-wide functional genomics methods.
  • Implementing high-throughput gene silencing via RNA interference (RNAi) screening.
  • Reviewing CRISPR/Cas9 gene-editing technology for functional screening applications.

Main Results:

  • Significant increase in the identification of novel drug target candidates.
  • Improved understanding of the relevance of genomic and molecular changes to diseases.
  • RNA interference screening established as a key functional genomic tool for target identification.

Conclusions:

  • Advanced genomic technologies are pivotal for personalized medicine and drug development.
  • RNAi screening offers advantages and presents challenges in target identification.
  • CRISPR/Cas9 shows promise as a future functional screening tool.