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Leveraging Human Genetics to Guide Cancer Drug Development
Ben Kinnersley1, Amit Sud1, Elizabeth A Coker1
1All authors: The Institute of Cancer Research, London, United Kingdom.
JCO Clinical Cancer Informatics
|January 18, 2019
Summary
Leveraging cancer genetic insights from genome-wide association studies significantly enhances precision oncology drug development and repurposing success rates. This data-driven approach improves drug approval predictions in preclinical and clinical trials.
Area of Science:
- Genetics
- Oncology
- Pharmacology
Background:
- High attrition rates in cancer drug development hinder precision oncology.
- Genetic insights from genome-wide association studies (GWAS) offer a potential solution.
Purpose of the Study:
- To evaluate if GWAS-derived genetic insights can guide cancer drug development and repurposing.
- To assess the enrichment of successful drug approval by integrating genetic information.
Main Methods:
- Identified 955 cancer genetic risk variants from GWAS catalog across 37 cancers.
- Linked variants to target genes using linkage disequilibrium, 3D DNA structure, and gene function/expression data.
- Assessed druggability of targets and drug development enrichment using Pharmaprojects database and machine learning.
Main Results:
- Incorporating genetic information showed a 2.00-fold enrichment for preclinical drug approval success.
- A 2.75-fold enrichment was observed for phase II targets.
- Identified 15 approved non-oncology drugs for potential repurposing.
Conclusions:
- Genetic insights from inherited cancer susceptibility studies are valuable for data-driven drug discovery.
- This approach can inform and improve the success of oncology drug development and repurposing strategies.
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