A new database is now available that may help speed up the identification of new targeted agents for several types of cancer. Identical twin brothers, Obi Griffith, PhD, and Malachi Griffith, PhD, have created a comprehensive database that matches thousands of disease genes linked to cancer with drugs that target those genes.
However, this new database is about much more than just science. For the brothers, who are both research professors at Washington University in St. Louis, MO, it is very much a personal issue. Their mother died of breast cancer 17 years ago, just weeks before their high school graduation.
The Griffith brothers have created a comprehensive database called the Drug-Gene Interaction database (DGIdb) that is user-friendly and may help lower cancer mortality in the near future.
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“DGIdb could help prioritize candidate genes from genome-wide screens for development of novel therapies. It could also help identify cases where an existing drug used for a particular type of cancer could be used in another cancer type where a subset of patients harbor specific mutations or gene amplifications,” said Dr. Malachi Griffith, in an interview with ChemotherapyAdvisor.com.
They got the idea for the DGIdb after they were repeatedly asked whether lists of genes identified through cancer genome sequencing could be targeted with existing drugs. In the past, this could only be accomplished through specially produced software.
Dr. Malachi Griffith indicated he and his brother Obi wanted to create a comprehensive database that was similar to a Google search engine for disease genes. He explained that previously, clinicians or researchers who wanted to find out whether disease genes could be targeted with drugs had to search piecemeal through scientific literature, clinical trial databases, or other sources. He added there is a great deal of interest today in knowing whether certain drugs can target mutated genes in particular patients or in certain diseases, such as breast cancer or lung cancer.
Until now, there has not been an easy way to locate that information. Details of the DGIdb were recently reported in Nature Methods, and the database currently provides a type of “one-stop shopping” for drug-gene interaction information.1 The database is weighted heavily toward cancer genes, but also includes genes involved in Alzheimer’s disease and other illnesses.
Identical twins Obi (left) and Malachi (right) Griffith have developed DGIdb, a searchable drug-gene
interaction database. Photo courtesy of Washington University, St. Louis.
The DGIdb includes information from 15 publicly available databases in the United States, Canada, Europe, and Asia. Users can enter the name of a single gene or multiple genes to retrieve drugs targeting those genes. The database also provides details on whether a given drug is an inhibitor, antibody, vaccine, or another type, and organizes genes of the druggable genome into two main classes: genes with known drug interactions, and genes that currently are not being targeted therapeutically but are potentially druggable, at least based on their membership in gene categories associated with “druggability” (eg, kinases).
The database is geared toward clinicians, researchers, and physicians who want to know whether mutations in disease genes, which have been identified through genome sequencing or other methods, potentially could be targeted with existing drug therapies.
Richard Wilson, PhD, Director of The Genome Institute at Washington University, in St. Louis, MO, said that the database is an invaluable new tool for oncologists working to design better treatment options for their patients. However, Wilson and his colleagues caution that the database is intended for research purposes and should not be viewed as means of recommending treatments.
After several years of development, the database is now is publicly available and free to use. DGIdb includes more than 14,000 drug-gene interactions involving 2,600 genes, along with the 6,300 drugs that target those genes. In addition, there are another 6,700 genes in the database that could potentially be targeted with future drugs.
According to Dr. Malachi Griffith, “DGIdb could be used to help stratify patients harboring specific genetic signatures by identifying the drugs that target specific mutated or over-expressed genes. Any clinical trial that is proposed to profile the mutation or expression status of a driver gene could use DGIdb to select therapeutic agents that inhibit or otherwise interact with that gene.”
