Stemming the Tide

Michigan’s universities are developing innovative new methods to detect and treat disease with inventions that are migrating from the laboratory to the marketplace

By Candace Stuart

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Illustration by James Yang

Drugs that target the root cause of cancer. Minimally invasive biopsies that tell surgeons in real time whether tissue is diseased or healthy. A faster, less-expensive, and greener process for making drugs.

These made-in-Michigan innovations are more than futuristic projects in academic labs. The potentially game-changing technologies are migrating from the University of Michigan, Wayne State University, and Michigan State University into the marketplace through the creation of companies and ties to industry. The projects of an oncologist, an engineer, and a chemist, respectively, each remains at the early stages of commercial development, though, and each faces challenges before becoming a mainstay in the clinic, operating room, or pharmacy. But success leads to better patient care, profits for the universities that own the patents, and new jobs for the region and state. It’s also part of the $36.7 billion the health-care industry contributes to Michigan’s economy in annual wages, salaries, and benefits.

“The universities are absolutely critical for ensuring that innovation and innovative technologies have the opportunity to be commercialized successfully,” says Stephen Rapundalo, executive director of the state trade association MichBio. “They’re the pivotal first step.”

Killing cancer at its source

Chemotherapy and radiation, the standard treatments for cancer, can be brutal on patients and sometimes offer a hit-or-miss approach for eliminating the disease. The outcome is especially dire for patients with advanced metastatic cancers — cancers that spread to other organs — as well as cancers that appeared to have gone away during treatment, only to reappear hardier than ever. This year, the University of Michigan Comprehensive Cancer Center expects to conduct clinical trials on two types of drugs that, theoretically, will be less debilitating to the patient and more devastating to the cancer.

The goal is to crush cancer at its root source — the stem cells. U-M oncologist and cancer center director Max Wicha and his colleague Michael Clarke first identified cancer stem cells in solid tumors about five years ago and, in 2004, launched a biotech company called OncoMed Pharmaceuticals to develop drugs that target the cells.

“Hopefully, we thought, it would be a better way to treat cancer,” says Wicha, a practicing clinician and researcher. “The dream is to come up with a new idea and see patients benefit from it.”

The conventional view of cancer is that cells either mutate or are genetically predisposed to become malignant, meaning they replicate beyond their normal confines to produce tumors. Malignant cells can also spread through the blood or lymph systems and colonize in distant organs. Chemotherapy treatment offers a scattershot approach for destroying rogue cells, while radiation is directed at specific tumors. It’s generally believed that any cancerous cells that fail to swallow chemo’s poison pill or wither under a radiation beam have the potential to repopulate.

Wicha and Clarke offer an alternative view. They argue that only a few cells in a tumor, meaning cancer stem cells, have the capacity to proliferate and form new tumors. Like normal stem cells, cancer stem cells make exact copies of themselves, as well as offspring like daughter cells that perform specific functions. All tissues have stem cells, and all stem cells have the potential to repeatedly self-replicate, whereas daughter cells that specialize will sputter out after a set number of cell divisions. (Neither cancer nor normal stem cells are embryonic stem cells, which are more of a cellular blank slate.)

Chemo might succeed in wiping out so-called daughter cells, which divide more frequently and are less robust than stem cells, but it can miss the cancer stem cells that drive malignancy, Wicha says. That’s why tumors may shrink or become undetectable, and then reappear. “They’re actually starting with a [stem] cell that has already evolved a tremendous amount of protective mechanisms,” he says. “That’s why it’s been so hard to cure cancer. It’s a tremendously hard job, and it still will be a tremendously hard job. If we begin to see why it’s so hard to kill cancers, then we can develop the right targets.” Wicha, a breast-cancer specialist, and Clarke, who is now an associate
director at Stanford University’s Institute for Stem Cell Biology and Regenerative Medicine in California, first identified cancer stem cells in 2003 embedded in breast tissue samples. In order to do so, they had to develop a method for separating cancer stem cells by finding markers or proteins on the outside of cells specific to cancer stem cells. U-M patented its invention, which is licensed exclusively to OncoMed. Since then, cancer stem cells have been found in myriad other cancers, including the brain, colon, pancreas, head, and neck.