The Possibilities For Personalized Cancer Treatment
By Jim Nicholson
A cure for cancer?
It’s a conundrum that has been facing medical science for as long as cancer has been an identifiable disease. Thanks to a recent development at the Genome Center at Washington University, a first-in-the-world breakthrough has occurred.
Cancer is a disease of the genes. Everyone is born with certain genetic risks for any number of diseases. Certain families—and virtually everyone knows one, however, are predisposed to develop cancer. Environmental factors increase the risk—exposure to the sun increases the odds for developing melanoma, smoking for developing lung cancer, et cetera. The odds of occurrence increase if one is from a family predisposed to develop cancer. To better diagnose, treat and cure cancer, medical science has long been attempting to find those genetic markers with which one is born, as well as those one develops through encountering carcinogens.
If medical science can determine what goes wrong in an individual’s genetic code to create or increase the risk of cancer, it can better treat the individual with the predisposition to developing a malignancy. Washington University’s School of Medicine’s Genome Center is one of only three entities in the country (the others are at the Massachusetts Institute of Technology and the Baylor College of Medicine in Houston) with access to state of the art technology, which, in layman’s terms, allows its researchers to avoid ten to fifteen years of preliminary research to advance contemporary medical knowledge. Genome Center Director, Dr. Richard Wilson, makes a fishing analogy to simplify the complexity of the research, “Instead of sitting in a bass boat, casting a single line hoping to land a fish, we’re kind of like an ocean trawler, casting giant nets at the genomes and aiming to land a massive catch in our attempt to find all mutated genes.”
Last year, with Dr. Timothy Ley, an oncologist in the Washington University School of Medicine and Dr. Elaine Mardis, Co-Director of the Center, the Genome Center became the first entity in the world to sequence a cancer genome; in this case, a genome from a woman in her mid-50s who died of acute leukemia. Using specific software and analytical tools, some of which the researchers developed specifically for the project, the team discovered 10 mutations in the patient’s genes—eight of which were found in genes that normally suppress tumor growth. One mutation was discovered in a gene family that is also involved in the development of embryonic stem cells.
“We learned a lot,” says Wilson, “and we can build on that.” Advances at the Genome Center seem to be the norm these days. It first sequenced the human genome in 2000; less than a decade later, it has been the first to sequence a cancer genome. The trawling analogy proves particularly adept here; of the nearly 2.7 million variants in the patient’s tumor cells, it was determined that the number of variants requiring further study numbered a mere 60,000. That the massive numbers involved proved workable demonstrates the highly specialized nature of the Center’s technical resources.
Human cancer is classified by tissue (or, in the case of leukemia, by blood cells). Each is specific to its organ—lung, breast, liver, brain, pancreas, prostate, et cetera—of origin. Adding to the complexity in researching the disease is the fact that there is not one specific cancer for each organ; instead, a multiplicity of cancers emerge under a simple heading of, for instance, brain cancer. “Most cancer patients,” relates Wilson, “receive specific treatments” for their generic (brain, breast, et cetera) cancers. Some, however, require differing treatments based on both the traits of the disease and the individual patient’s reaction to both the disease and the specific treatment.
By being able to examine each patient’s individual DNA and by looking at the entire history of each patient’s course with the disease, doctors will be able to personalize the treatment to increase the odds of success and minimize undesirable side effects. Anyone who has been privy to a friend or family member reeling from the side effects of “bad chemo” recognizes the relief inherent when a “good chemo” is located. Imagine doctors being able to both instantly prescribe both the “good chemo” and the most effective treatment for each patient. That is why the sequencing of a specific cancer genome is so important; it opens the possibility of developing better drugs with specific targets to treat the disease. “We’re now two, three, four…ten years away,” relates Wilson, “depending on the specific genes involved.” The Genome Center’s discovery, in relation to personalized cancer treatment, has turned the art of the medically possible into the art of the medically probable.
