02:31am Friday 10 April 2020

Understanding the Connections Between Cancer and Inflammation

For Anna Huttenlocher, MD, the promise of that weapon makes perfect sense, as she has studied the intimate relationship between cancer and the immune system for the past 16 years.

“I have a long-standing interest in the parallels between cancer and immunology,” Huttenlocher says. “There is growing evidence that we should treat some cancers more like we treat a chronic autoimmune disease: with regular low-dose or more targeted drugs, instead of high-dose blasts of aggressive chemotherapy.”

Huttenlocher is a Vilas Distinguished Achievement Professor of medical microbiology and immunology at the University of Wisconsin–Madison and the UW Carbone Cancer Center. As the director of the Medical Scientist Training program, she is passionate about educating the next generation of physician-scientists, and regularly sees patients as a pediatric rheumatologist with UW Health.

At the center of Huttenlocher’s research is cell migration: the molecular mechanisms that control the movement of both immune and tumor cells. By studying the similarities and differences between these moving cells, she hopes to help prevent the metastatic invasion of new tissue that is often responsible for cancer’s fatal outcome.

“If we know more about a drug’s interaction with different cell types within a living organism, and how that interaction varies over time, we may be able to optimize treatments for human disease. To me, this type of system biology is a particularly intriguing area of cancer research,” Huttenlocher says.

Her favorite model organism for studying these cellular interactions is the zebrafish: a tropical freshwater fish about as long as a human pinky finger that develops from a fertilized egg to an adult outside the female. Since the egg and the young embryos are completely transparent, the cellular response to drugs over time can be directly observed inside the whole animal.

“We can now put a patient’s tumor cells into a zebrafish to test whether a drug is able to prevent cancer progression,” Huttenlocher says. “That is likely to be better than studying human cells in a culture dish. It is potentially a very powerful tool for personalized medicine, in which we would be able to tailor treatments based on the specific response of the patient’s tumor.”

Huttenlocher also hopes that zebrafish will help identify the best drugs for the patients she sees every week: children with autoimmune diseases, such as lupus and juvenile arthritis. Since the chronic inflammation that is part and parcel of these conditions also puts her patients at an increased cancer risk, the drugs she prescribes have a dual benefit: they mitigate disease-specific symptoms and may also lower the risk of tumor formation by reducing inflammation. The connection between cancer and the immune system is powerful enough that clinical trials are now underway to evaluate whether anti-inflammatory drugs like aspirin may help prevent cancer in people at increased genetic risk, such as patients with Lynch syndrome.

“A baby aspirin a day may be beneficial for many people,” Huttenlocher says. “If the ongoing trials support that possibility, it would be very exciting.”

University of Wisconsin School of Medicine and Public Health


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