Pharmacogenetics, the use of genetics to aid in personalized medicine, will match patients with the optimal pharmaceutical drugs. Source: http://www.flickr.com/photos/stewdean/
On Tuesday, January 27, Gregory Tsongalis, a professor of pathology at Dartmouth’s Geisel School of Medicine, gave a lecture on the developing field of molecular diagnostics. Over the last few decades, scientists have developed increasingly sophisticated molecular biology techniques involved in DNA sequencing. Molecular diagnostics is the application of these techniques to study, diagnose, and develop treatments for human diseases.
Tsongalis highlighted pharmacogenomics, the use of genetic information to prescribe medicine, as one rapidly emerging clinical application of molecular diagnostic testing. When patients take a drug for an illness, their bodies must be able to absorb, distribute, metabolize, and excrete it properly. These functions are controlled by enzymes, which are affected by genetic polymorphisms that vary from person to person. Thus, each patient’s reaction to a drug will be different depending on his or her genetic makeup. Citing that adverse reactions to drug therapy are the fourth leading cause of death in the United States, Tsongalis stressed that one drug does not fit all. He noted that, with the growth of molecular diagnostics, there is a trend towards personalized medicine that uses patients’ genetic information to prescribe the right drug at the right dosage.
Pharmacogenomics also gives doctors the capacity to construct targeted drug therapies. This ability is particularly useful in the field of oncology, where most current cancer treatments have minimal efficacy. Even drug therapies that show signs of success often cause severe adverse reactions. Tsongalis asserted that the current method of classifying cancers by tissue of origin is misleading, as each tumor is different at both the gene and protein level. Tumors originating from the same tissue can vary in genomic alterations, while tumors from different tissues of origin can have similar genomic profiles. Tsongalis suggested that in the future doctors should tailor personalized drug therapies to treat individual tumors instead of treating cancer as one disease.
According to Tsongalis, drug therapies can be developed based on genes found in tumors from molecular testing. Since adopting a new technology called Next-Generation Sequencing (NGS), his lab has been able to overcome sequencing limitations in scalability, speed, and resolution, granting his lab access to an unprecedented amount of genetic information. In August 2013, he used NGS to sequence about 93 percent of tumor samples, which he used to build genetic profiles for tumors. Some of the mutations in his tumor profiles were in known cancer genes that can be targeted in drug therapies. Many more, however, were “non-actionable” mutations in enzymes that are not amenable to pharmacological treatment. The lack of actionable mutations is one problem molecular diagnostics will have to tackle in the future if pharmacogenomics is to become a central feature of cancer treatment.