Pathway Understanding Key to Cancer Drug Discovery

As the Genetics Society of America's Model Organism to Human Biology (MOHB): Cancer Genetics Meeting in Washington, D.C. drew to a close, it was clear that the mantra for drug discovery to treat cancers in the post-genomic era is pathways. Pathways are ordered series of actions that occur as cells move from one state, through a series of intermediate states, to a final action. Because model organisms – fruit flies, roundworms, yeast, zebrafish, and others – are related to humans, they share many of the same pathways, but in systems that are much easier to study. Focusing on pathways in model organisms can therefore reveal new drug targets that may be useful in treating human disease. "By reading evolution's notes, we can discover what really matters in the genome," keynote speaker Eric Lander, Ph.D., founding director of the Broad Institute of Harvard and MIT and professor of biology at MIT, told a packed crowd at the MOHB: Cancer Genetics Meeting on June 19, 2012. What matters the most in the genome of a cancer cell may be the seeds of drug resistance, the genetic changes that enable cells to evade our best drugs, Bert Vogelstein, M.D., director of the Ludwig Center at Johns Hopkins University and an investigator with the Howard Hughes Medical Institute and a keynote speaker on June 17, told participants. He called drug resistance to single agents a "fait accompli," as a side effect of the evolution of cancer. "About 3,000 resistant cells are present in every visible metastasis," said Dr. Vogelstein. "That's why we see resistance with all therapeutics, even when they work. And we can't get around it with single agents.
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