For the past 26 years, Dr. Richard Terek has been treating bone cancer patients at Rhode Island Hospital in Providence.
Some forms of the disease respond fairly well to treatment, but one rare type of bone cancer is notoriously resistant to intervention.
Chondrosarcoma begins in the bones and spreads if not caught in time. Its stubborn tumors can be surgically removed, but if they take root in areas that are inoperable, the disease is often terminal.
“For chondrosarcoma patients, there’s no effective systemic treatment to stop the tumor from spreading,” said Terek, who is chief of musculoskeletal surgery at Rhode Island Hospital. “Surgically you can remove the tumors, but then sometimes they have already metastasized to the lungs. … If it does recur or show up in the lungs, there’s not a whole lot we can do.”
Terek, along with Qian Chen, director of the Center of Biomedical Research Excellence in Skeletal Health and Repair at Rhode Island Hospital and a professor of orthopedic research and medical science at the Warren Alpert Medical School of Brown University, are targeting the cancer with a long-term project that has begun to gain national attention.
“One big challenge for this type of cancer is that chemotherapy is very often not effective and radiation therapy also has a very limited effect, so basically there is no effective drug right now,” Chen said.
‘The strategy now is to try to make the cancer into a chronic disease.’
DR. RICHARD TEREK, Rhode Island Hospital chief of musculoskeletal surgery and bone cancer researcher
Funded by the National Institutes of Health, Chen and Terek have developed tiny carriers, or nanoparticles, that burrow their way into chondrosarcoma tumors and deliver medicine designed to inhibit their growth.
The goal, Terek said, is to manage the disease by slowing its progression and attacking the “biology” of the tumor.
“The strategy now is to try to make the cancer into a chronic disease, to keep it at bay and in check and suppressed for as long as possible,” he said.
Terek and Chen outline the project in a paper published in November’s Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research, but the two have been partnering on the work for the past decade.
Their research has focused on identifying which cancer cells to target and optimizing delivery technology to get growth inhibitors, or nucleic acid therapeutics, into tumor tissue, Chen said. Current experiments are centered on identifying the most efficient combination of nanoparticles and developing medicine, or “biologic therapeutics,” to piggyback on nanoparticles to take direct aim at chondrosarcoma.
Although Chen and Terek said the work is still in developmental stages, tests on cells from mice and those taken from human tumors have proved promising.
“The next step is really, in terms of drug development, to show that it’s safe in human patients,” Chen said.
Fundraising looms as the largest obstacle, Terek added.
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Chen and Terek at work in their Providence lab. / PBN PHOTO/MIKE SKORSKI[/caption]
Clinical trials “are hugely expensive undertakings that would require venture-capital investments,” he said.
Although trials involving human patients may be years away, the process, once it begins, may be expedited due to chondrosarcoma’s classification as an “orphan disease,” Chen said.
Normally, clinical trials are split into a first phase, which measures safety, and a second phase that tests efficacy. Since the treatment is targeting a rare disease, the two phases can be combined. Still, “the barrier is the right [amount of] funds. Once we have the funding, the clinical trials will take several years,” Chen said.
Chondrosarcoma affects fewer than 1,000 patients a year nationwide, with about one or two cases appearing in Rhode Island annually. Typically, the disease affects adults, Terek said.
In order to recruit a sufficient number of patients, treatment trials will need to include a number of institutions and large cancer centers across the country.
In the meantime, nanoparticles, with their ability to ferry drugs to intended targets, are versatile enough for numerous roles involving chronic diseases and other types of cancer.
In addition to patenting the process, Chen created NanoDe, a startup that will license the delivery platform technology through Rhode Island Hospital. The team has also grown to include a chemist, tasked with performing more extensive research into honing the particles’ ability to deliver drugs to tumor tissue.
“We have other applications, including post-traumatic osteoarthritis and rheumatoid arthritis, using this drug delivery technology. This can be used for the treatment of multiple diseases,” Chen said. “The chondrosarcoma treatment is the first one, but it’s not the last one.”
Correction: An earlier version of this story incorrect attributed the founding of NanoDe. Qian Chen created NanoDe.