Solving Sarcoma with a Drug Delivery Microdevice
Once researchers began to better understand the pathology of sarcoma, they also uncovered the biggest challenge in treating the disease — sarcoma tumors are among the most molecularly diverse types of cancer. Rather than affecting a single organ or system in the body, sarcomas show up practically anywhere. Their rarity and heterogeneity make studying the disease difficult because very few medical institutions treat the volume of patients needed to conduct therapeutic studies.
The University of Texas MD Anderson Cancer is the exception. Seeing more than 6,000 sarcoma patients annually, MD Anderson researchers have identified an opportunity to leverage new technology in a way that will revolutionize the way in vivo sarcoma studies are performed.
Finding effective therapeutic interactions is an informed, but still trial-by-error approach. Patients simply do not have the time, and health care systems do not have the resources, to apply several rounds of ineffective therapies. Imagine if an investigator could safely test 16 therapies at once and measure their effect directly at the tumor site. And do all this in 24 hours. We now have that technology thanks to a partnership between Joseph Ludwig, M.D., associate professor of Sarcoma Medical Oncology, and biotechnology researchers at the Massachusetts Institute of Technology.
A new implantable microdevice prototype is essentially bringing the laboratory into the patient’s body, preserving the native tumor physiology for the most accurate therapy testing possible. The device is cylindrical, measures 4 mm in diameter and is delivered directly into a tumor through a biopsy needle. Up to 16 reservoirs are filled with single agents or drug combinations in amounts less than one millionth of a systemic dose. The U.S. Food and Drug Administration does not regulate these microdoses as strictly as it does full-dose experimental therapies, allowing researchers to be more opportunistic (while still monitoring safety) and evaluate therapies faster. Both the device and a small region of surrounding tissue are then removed 24 hours later under the guidance of ultrasound imaging. Pathologists can then use fluorescent microscopy to evaluate the anti-tumor activity of many therapies and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to evaluate non-fluorescent drugs. Each compound is directed to a restricted tissue section, so there is no cross-contamination between therapies. Evaluation is individual and precise.
The only other clinical location testing this microdevice is Memorial Sloan Kettering Cancer Center, but they are focusing on breast cancer and ovarian cancer patients. MD Anderson faculty would like to make the device available to sarcoma patients. Dr. Ludwig will oversee the microdevice’s use in adult sarcoma patients, and Najat Daw, M.D., professor of Pediatrics, and Branko Cuglievan, M.D., fellow of Pediatrics, will manage its use in younger patients (10 and older).
Cost is still prohibitive for universal use of the microdevice — there are unfunded expenses related to manufacturing, preparation, the drugs themselves, insertion, removal under anesthesia and molecular analysis of therapeutic efficacy. An early investment would help the MD Anderson team scale production to bring initial costs down. Once effectiveness is proven, subsequent investment will surely see this technology through wider adoption. Beyond serving as a game-changer for the development of future drug development, this microdevice will impact lives immediately, personalizing therapy for each individual sarcoma patient.