Translating Today's Discoveries

Taking on the challenge of lung cancer, one tiny worm at a time

C. elegans wormsBy implanting human cancer mutations into tiny C. elegans worms, researchers are helping find out which genes make promising drug targets.

In the wild, C. elegans is practically invisible. Barely a millimeter in length, these tiny worms burrow in soil and compost heaps. Yet in lung cancer specialist Dr. Ravi Salgia's laboratory at the University of Chicago Medicine, they're helping to dig up more personalized cancer treatments.

"C. elegans turned out to be a very powerful tool," said Salgia, MD, PhD, the vice chair for translational research in the Department of Medicine. For the past decade, he and his team have been pinpointing genetic abnormalities that occur in patients' lung cancer tumors.

As the first researchers to implant human cancer mutations into the worm and observe its effects, his team can more quickly determine which genes make promising drug targets. It's a pioneering approach that often takes only a few weeks, versus the year or more required for more traditional experiments.

Laboratory discoveries by University of Chicago Medicine scientists are leading to a better understanding of the biological basis of cancer and personalized therapies.

"What we want are better answers faster," said Salgia, who also is the associate director for translational sciences for the University of Chicago Medicine Comprehensive Cancer Center. That means not only speeding up the research process with novel experimental models like C. elegans, but also bringing the latest genetics-based findings directly to cancer patients through more personalized therapies and clinical trials.

"From years of research done at the University of Chicago and elsewhere, we have learned that each person's tumor is unique," said Richard L. Schilsky, MD, professor emeritus at the University of Chicago Medicine and chief medical officer of the American Society of Clinical Oncology (ASCO). "Our goal is to understand what makes a patient's tumor tick at the molecular level and, based on that knowledge, deliver the best available therapy for that individual."

Recently, for example, Salgia treated a patient whose tumor had already spread beyond the lung. Rather than starting chemotherapy, once standard for advanced lung cancer, Salgia did a molecular-level analysis of the tumor tissue and discovered a rare mutation, called ALK translocation, was fueling the cancer cells.

 Ravi Salgia, MD, PhD Ravi Salgia, MD, PhD in his lab

"There's a specific targeted therapy that works against that," explained Salgia, who spearheaded clinical trials for the drug at the University of Chicago Medicine in 2010. The therapy, now known as crizotinib, was approved by the FDA in August 2011 and is just one example of how the University of Chicago Medicine is giving cancer patients access to more powerful personalized treatments, often before they are available elsewhere.

"It's very important that patients and their families realize that just having a lung cancer diagnosis may not be enough," Salgia said. "We ask, 'What kind of lung cancer?' Then, based on the genetic abnormalities that can occur, we design the treatment appropriately."

Meanwhile in his lab, the researcher-clinician continues to narrow the gap between understanding how tumors work and what will stop them in their tracks. With every mutation he studies in C. elegans, Salgia knows he's creating a more promising future for patients.

"We take pride in taking care of our patients," he said, "but we also take pride in making sure we can do state-of-the-art research and then combine the two to provide even better care."

Imagine cover

This story originally ran in the Fall 2012 issue of Imagine, a quarterly magazine published by the University of Chicago Medicine.
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