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Pharmacogenetics and Cancer Therapy

© David Olle

The choice of drugs to treat patients has often been described as an art rather than a science due to the great variability in response that is seen among patients. While many patients are cured of their conditions, others do not respond or exhibit toxic reactions to the treatment. Many factors can lead to a variable drug response, including diet, environment, gender, age, and health status. However, by the late 50's physicians realized that there was a genetic basis for much of this variability. In 1959, Vogel coined the term pharmacogenetics, which is the study of how genetic variations affect drug response. With the recent completion of the Human Genome Project, the field has been rapidly developing, since it greatly facilitates the detection of these genetic markers of disease.

The basis for pharmacogenetics 6

Genes, the basis for heredity, reside in the DNA molecule. The DNA molecule consists of units called nucleotides, which contain one of four different nitrogenous bases. The DNA molecule contains many genes, which are defined stretches of DNA with a specific sequence of nucleotide bases containing instructions for the synthesis of a protein. The genome of a person consists of all the genes that are present in its DNA. Polymorphism, which means "many forms," refers to differences in sequence at a specific location on the DNA that are observed among individuals. These location differences are also known as alleles. Single nucleotide polymorphisms, or SNPs, are the most common type of genetic variation. Currently, there is an intense research effort taking place to determine which of these polymorphisms have relevance to the treatment of human diseases.

How pharmacogenetics relates to cancer treatment

Cancer chemotherapy is characterized by a narrow range of drug dosage that is effective for treatment but not toxic. In order to be effective, the drug must reach the cancer cells in an active form, and be retained within the cells for a long enough time to do its work. After the cancer cells are destroyed, the chemotherapeutic drug must be disactivated and eliminated by the body before it becomes toxic. In terms of cancer, researchers must consider polymorphism in both the host (normal body cells) genome as well as in the tumor genome. Gene instability is the hallmark of cancer, and continuously evolves as the cancer progresses. Therefore, gene study in cancer is more centered on determining which genes are expressed at a certain point of time, rather than determining SNPs, which are stable characteristics of genes.