Say you get diagnosed with cancer. Your doctor gets you a blood test, sends the results in, and before long, you get back a sheet that tells you exactly what drugs will best fight the disease - essentially giving you a roadmap toward curing your illness. Sounds like Gattaca stuff: sending in your genome to get back a reading as to exactly how drugs will interact with your system? Well, it still is science fiction - for now.
Recent research from The International Warfarin Pharmacogenetics Consortium, published in the Feb. 19 issue of the New England Journal of Medicine with contributions from the University of Florida, detailed how genetic information led scientists to better prescribe accurate and effective doses of an anticoagulant. It has been known for quite some time that background genetic variability plays a key role in dose determination for most drugs, but this study has finally acquired the statistical data needed to support the conclusion that this genetic approach to drug prescription and interaction may be a realistic possibility, and for more than just anticoagulants.
Anticoagulants are a far cry from cancer-busting prescriptions, but the technology used to determine the correct dose - genomic collection, analysis and compatibility screenings with drugs - are clear first steps toward more far-reaching applications.
The drug in question in the survey is the very widely-prescribed anticoagulant Warfarin. It was first used in high doses as a pesticide, but physicians noted that, under proper dosage, it was very safe for humans and did wonders in preventing thrombosis and embolisms. Now, it is the most commonly used anticoagulant drug; it is used to treat blood clots by thinning the blood (preventing coagulation) and for therapy after atrial fibrillation, heart valve replacements, and even heart attacks.
The only problem with Warfarin is that it's a highly sensitive anticoagulant; push the dose too high, and what was helping before is now hurting you. There is a reason it was used as a pesticide first; if the blood is thinned too much, it could cause uncontrollable bleeding, like in anemia, and other serious side effects. "Warfarin is a complicated drug to use because of its very narrow therapeutic window," Julie A. Johnson, who directs the University of Florida Center for Pharmacogenomics, said. "This is one of the top five drugs that cause hospitalizations for adverse effects."
Enter dose management. By analyzing the genome of a patient and seeing how compatible it is with Warfarin, a doctor could, in tandem with the normal tests (height, weight, medical history), provide an appropriate dose for a specific patient without undue risk of overdose.
"In this study, we used data from the largest, most diverse group of patients to date to develop a method for using genetic information in combination with other patient information to determine the dosage of a very commonly used drug," Johnson said. Over 4,000 candidates were screened in the survey and matched with specific drug doses based on their genotypes. Based on the results, the study was able to predict with significant accuracy the effective dose of the drug.
This may not seem overwhelming and is certainly nowhere near the Gattaca-esque technology mentioned in the first paragraph. But this kind of drug prescription based on genetic compatibility is what some scientists are banking on to usher in the next wave in drug therapies, especially for cancer.
In an article published last May, drugs tailored for specific cancer types showed greater effectiveness in treating lung cancer in a study described in the Journal of Clinical Oncology. This study focused on cancers that had specific mutations in the EGFR receptor, a surface protein that, on some lung cancers, can acquire a specific mutation. In it, a drug targeted to that specific mutated surface receptor was administered to see if genetically determined treatment could work. In the study, over 55 percent showed immediate reduction in tumor size, and all but two (which were later found to have slightly different mutations) had reduction or stabilization in tumor size for the entire month of the trial.
These studies both demonstrate the same thing: genetic information can determine treatment regimens of drugs specific to the individual, at least sometime down the road. Right now, we don't have the broad-based genetic information needed to design more far-reaching and meaningful drugs. For now, this exciting possibility is confined to the realm of studies and conjecture. But as we have seen with these two studies, the potential of genetically targeted drugs is very real and could become a powerful and life-saving tool against a variety of diseases.
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