Interdisciplinary Team Awarded $3.4 Million to Research Safer, Improved Chemotherapy

Armed with a new $3.4 million grant from the National Cancer Institute (NCI), an interdisciplinary research team of Sylvester Comprehensive Cancer Center members is creating a blueprint that may help to deliver safer, more-effective chemotherapy, with far fewer long-term negative health consequences.

Roland Jurecic, Ph.D., associate professor of microbiology and immunology, and cell biology at the University of Miami Miller School of Medicine, is the principal investigator. His research focus is on the biology of hematopoietic stem cells (HSCs) — cells that continuously produce new blood and immune cells — and the effects of cancer therapy and infections on HSCs and the hematopoietic system.

He explains that when cancer patients hear the long-awaited words, “your cancer is gone,” many of them still face new challenges down the road. “Serious and permanent damage to the heart, lungs, blood cell forming, immune, gastrointestinal, reproductive, central and peripheral nervous systems can result from chemotherapy, and many of these conditions impair the long-term health of cancer survivors and can be life-threatening,” said Jurecic.

Prior to this new research effort, organ- and system-specific chronic adverse effects of chemotherapy had not yet been systematically investigated. “Unfortunately, this damage is not always immediately detectable,” said Jurecic. “For months or years after completion of chemotherapy there may be no signs that the hematopoietic and immune systems of cancer survivors are compromised. It takes another injury with chemicals, radiation, or strong viral or bacterial infection for these symptoms to become apparent.”

More important, while the pediatric cancer survivors receive long-term health follow-up, adult cancer survivors most often do not. “This must change, since therapy-induced complications get worse with aging,” said Jurecic.

According to a 2016 report by the American Cancer Society and NCI, there are already 15.5 million cancer survivors in the U.S. That number is expected to grow to more than 20 million by 2026, when an estimated 75 percent of cancer survivors will be over 65 years of age. Adult and elderly cancer survivors have multiple complex health conditions arising from both therapy after-effects and aging.

“Continued growth of the cancer survivor population and their increased primary health care utilization will have a far-reaching impact on the health care system in America,” Jurecic said. “Research is needed to minimize or prevent the collateral damage that cancer treatments leave behind.”

His research team includes experts in viral immunology (Samita Andreansky, Ph.D., assistant professor of pediatrics), development, function and aging of the immune system (Richard L. Riley, Ph.D., professor of microbiology and immunology), and tumor immunology and targeted chemotherapy (Paolo Serafini, Ph.D., assistant professor of microbiology and immunology).

Supported by the UM Interdisciplinary Team Science Pilot Program grant, this team previously generated data showing that chemotherapy treatment for breast cancer significantly impairs both HSC function and the responses of the hematopoietic and immune systems to primary and recurring viral infections.

“When healthy, our immune system has a natural ability to ‘remember’ past ailments it faced,” said Jurecic. “When you get the flu, for instance, your immune system creates memory cells. Should you encounter the same type of influenza again in the future, the job of these cells is to mount fast and more-efficient immune reactions to eradicate the virus. But if your protective immune cell memory is damaged, you are at risk for severe complications, including hospitalization and death, from seasonal influenza and pneumococcal bacteremia.”

According to Jurecic, chemotherapy causes extensive cell damage, which in turn causes intense chronic inflammation. The inflammation can then permanently impair the function of many surviving cells, such as HSCs and immune memory cells. The NCI-funded research will focus on finding ways to significantly reduce inflammation during and after chemotherapy, to see if such an approach can safely minimize or prevent long-lasting adverse effects.

The team’s first step will be to build a comprehensive blueprint of cancer therapy damage to hematopoietic and immune systems. They will further study the systems’ responses to additional stress and injuries, such as primary and recurring viral and bacterial infections. This blueprint will help to identify the mechanisms causing therapy-induced damage, such as chronic inflammation. It will also identify targets for therapeutic drug intervention.

In the next phase, the team will test combined treatment with chemotherapy and different FDA-approved and novel non-steroidal anti-inflammatory drugs (NSAIDs). They will also test combined treatment via novel intra-tumoral-delivered chemotherapy drugs with and without NSAIDs.

They’ll then study pediatric cancer survivors in collaboration with the pediatric oncologists at Sylvester. By translating their findings into clinical trials, they will be able to test the safety and efficacy of new cancer treatment approaches.

“Long-lasting adverse effects of cancer therapy still threaten growing populations of cancer survivors,” said Jurecic. “Our overarching goal is to accelerate the development and implementation of treatments that will safely minimize or prevent these issues.”

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