Cancer cells hijack many different kinds of normal systems in human cells and use them to grow malignantly, including food sources, growth, and normal cell death.
They also hijack normal tumor-suppression systems inside cells, thwarting them so that the mutated cells can grow limitlessly without interference. Some of these natural tumor suppressors consist of small bits of genetic material, called microRNAs, which help regulate a cell’s growth. In theory, restoring microRNA tumor suppressors to cancer cells could be a powerful weapon against cancer, but the challenge has been delivering them where they are needed.
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Cancer cells hijack many different kinds of normal systems in human cells and use them to grow malignantly, including food sources, growth, and normal cell death.
They also hijack normal tumor-suppression systems inside cells, thwarting them so that the mutated cells can grow limitlessly without interference. Some of these natural tumor suppressors consist of small bits of genetic material, called microRNAs, which help regulate a cell’s growth. In theory, restoring microRNA tumor suppressors to cancer cells could be a powerful weapon against cancer, but the challenge has been delivering them where they are needed.
Now a polymer chemist at the University of Texas Southwestern Medical Center is figuring out how to deliver these natural tumor suppressors by encapsulating them in nanoparticles.
Daniel Siegwart was recruited in 2012 from the Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT. He joined the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center.
Lung cancer is the leading cause of death from cancer in the U.S., with treatment involving radiation and chemotherapy that kill all rapidly dividing cells indiscriminately, often with devastating side effects. Survival rates haven’t improved in nearly three decades.
Treating lung cancer with microRNA therapy is a promising approach, which would harness a cell’s natural growth restriction mechanisms, but until now has run up against a number of barriers. Getting them into the right cells without having the material degrade en route, and without causing any toxicity elsewhere in the body, has been daunting.
Siegwart and his lab have developed biodegradable polymer nanoparticles that can encapsulate a microRNA and deliver it to its intended target. His approach has proven successful in mice bearing human lung tumors.
To find the right polymer, Siegwart synthesized thousands of related materials and tested how well they got inside cells, how well they encapsulated the microRNA, and how toxic the polymer nanoparticles were in the liver.
By testing the polymer nanoparticles side by side in normal and cancerous cells taken from the same patient, he discovered a nanoparticle that would only enter cancer cells. “Because the biology of a cancer cell is different from a normal cell,” he says, “we found that cancer cells are able to internalize a specific chemical nanoparticle much better than normal cells.”
Siegwart also made the polymers so that they degraded naturally inside the liver and toxic levels could never build up.
In animal models, he found that not only could he treat lung cancer, but also liver cancer and ovarian cancer. Even aggressive forms of cancer responded much better to the microRNA therapy than to the current standard of care.
Siegwart has filed a patent related to his research and has hopes of commercializing the technology to make it available for clinical trials in patients.
He has received nearly $2.4 million in follow-on funding for his research, from the American Cancer Society, Shelby Pancreatic Cancer Research Grant Program, Department of Defense, The Mary Kay Foundation, Welch Foundation, and UT Southwestern Translational Pilot Program.
He says the CPRIT funding enabled him to create 15 jobs in his Texas laboratory. He finds the research culture at UT Southwestern Medical Center equivalent to traditional research powerhouses, like MIT or Harvard, but with the added bonus of all of Texas’s culture and uniqueness.
Siegwart received his undergraduate degree in biochemistry from Lehigh University, and his Ph.D. in chemistry from Carnegie Mellon University. He began his postdoctoral training in chemical engineering at MIT in 2008.
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