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Patients and their physicians have quite a few treatment options to sort through to manage hepatocellular carcinoma, the most common form of liver cancer.
Physician-scientists from Mayo Clinic, in collaboration with Harvard University, report in Science Translational Medicine that they were able to uniformly distribute a chemotherapy drug in preclinical models into liver tumors and other solid tumors.
Generally, a liver transplant is considered the best option, but when a liver is not available, other treatments include drugs, surgery to remove the tumor, or targeted therapies to destroy cancer cells. Targeted therapies, also called local-regional therapy, are ones that use extreme heat or cold, radiation, or chemotherapy to destroy tumor cells.
These targeted therapies, used to bridge a patient from diagnosis to transplantation, are limited to certain areas of the liver — for example, places away from other structures that could be injured, like the gallbladder. Another problem with liquid chemotherapy agents is that they may not saturate the tumor, thereby missing some cancer cells and paving the way for recurrence.
"No matter how you deliver the drugs today, they wash away. They fail to uniformly distribute. This is the Achilles' heel of cancer treatment," says Rahmi Oklu, M.D., Ph.D, a vascular and interventional radiologist at Mayo Clinic and senior author on the paper. But Dr. Oklu, who is the founder and director of the Minimally Invasive Therapeutics Laboratory at Mayo Clinic in Arizona, has developed a potential fix.
The substance is called an ionic liquid, which is a type of electrically charged fluid ― a salt in a liquid state. Ionic liquids are thick, syrupy fluids that conduct electricity and do not evaporate.
The team combined chemotherapy drugs with an ionic liquid containing a blend of chemicals, including choline and geranic acid.
Dr. Oklu first heard of this combination at a talk given by Samir Mitragotri, Ph.D., of Harvard University. Dr. Mitragotri was using ionic liquid to deliver insulin through the skin. Intrigued by this observation, Dr. Oklu thought of liver cancer right away because it's difficult to punch through the cell membrane and the dense connective tissue of these tumors. And it's important that these tumors are treated.
"If you don't treat these tumors, then the patients can fall off the transplant criteria, so they can't get a transplant," Dr. Oklu says. "You could do microwave ablation and basically burn the tumor, but you can't do it next to the heart or other important structures, and it depends on the number and location of the tumors."
In the paper, the authors report that they were able to consistently ablate and distribute a chemotherapy drug uniformly throughout human tumors of different origins, as well as liver tumors in animal models. The drug spread circumferentially, encircling the tumor and remaining in the ablation zone for the length of the 28-day trial. In current therapy, Dr. Oklu says, the drugs often wash away fairly quickly. The ionic liquid, which the authors call a "locally active agent for tumor treatment and eradication," or LATTE, also encouraged immune cells to infiltrate the microenvironment of the tumor.
This study was funded by the National Institutes of Health. Drs. Oklu, Albadawi and Mitragotri declared that they are inventors on a patent application submitted by Mayo Clinic that covers LATTE and its applications. You can find a full list of disclosures in the paper.
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