A microdevice implanted into a tumor could release up to 100 individual cancer therapeutics or combinations and, upon retrieval from the tumor, could identify the best treatment option for that tumor, according to findings presented at the annual meeting of the American Association for Cancer Research, held from April 16 to 20 in New Orleans, Louisiana.
Researchers have initiated a clinical study to test the safety and feasibility of placing and removing the microdevice in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer.
“Currently, there are about 150 cancer drugs approved by the U.S. Food and Drug Administration, and many cancer patients have different drugs to choose from to treat their specific disease,” said Oliver Jonas, a postdoctoral fellow at the Massachusetts Institute of Technology. “However, patients respond differently to different drugs, and often, no two patients have the same response to a specific drug. It has been a major challenge to determine which drug or combination of drugs to give to which patient. Being able to identify the right therapy that will work optimally for every patient will be a major advance.”
Jonas and his colleagues engineered a small implantable microdevice that is less than 1 mm in diameter and about 4 mm in length, which has multiple reservoirs to hold single agents and combination therapies. The device is implanted into the tumor through a small biopsy needle and is left there for about 24 hours. The implant is then extracted along with a layer of surrounding tumor tissue, and the tissue is analyzed to determine the effect of each of the drugs and combinations on the tumor.
“We published a study last year in Science Translational Medicine, in which we demonstrated that we can implant this microdevice into mouse tumors and that we can test 16 different therapies. We’ve increased that number to 100 since then,” Jonas said. “We showed that the local readout that we can get from many agents in a single tumor is actually predictive of the drug sensitivity.”
The researchers engineered the tiny, cylindrical microdevice using biocompatible plastics. When implanted in a mouse tumor, the therapeutics, loaded in reservoirs within the device, were released in such a way that “crosstalk” between the different drugs was eliminated. The researchers also adjusted the drug-release rates to mimic the concentration of the drug achieved by standard systemic delivery, Jonas explained.
In addition to further developing the device to hold up to 100 different drugs and combinations, the investigators are able to study the tumor via real-time imaging while the device is still in place. This is accomplished via optical fibers attached to each reservoir, Jonas added.
“We are now able to measure how tumors adapt and change when they are treated locally or systemically, and how their sensitivity to different drugs changes when switched from standard-of-care therapy,” Jonas said.
He explained that, traditionally, there are two approaches to systems biology; one approach is to study the effects of multiple drugs on one type of cell in the laboratory, and the other is to conduct mouse studies in which only one or two agents can be tested at a time.
“We are showing that there is a middle ground where one can work in vivo, so that we take into account the effects of the microenvironment, but can also screen 100 or more compounds efficiently and rapidly in a single tumor, such that we can prioritize therapy to a patient, in addition to being able to understand the cancer in a functional way that we haven’t been able to do before,” Jonas said.
Source: AACR; April 19, 2016.
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