特殊分子直达肿瘤疗法有望问世

Finding and treating a tumor without disturbing normal tissue presents challenges – sometimes the most effective therapies can be invasive（侵入的，攻击性的） and harsh（粗糙的，严厉的）. Researchers at Duke University Medical Center have devised a way they might deliver the right therapy directly to tumors using special molecules, called aptamers（适体，配体）, which specifically（特定的，明确的） bind to living tumor tissue.

They screened a large pool of aptamers in a rodent（臼齿类的） with liver cancer until they found the best molecule to bind to a tumor protein.

"We are already exploring attaching chemicals to the aptamers, so the aptamer molecules could deliver tumor-killing agents where they are needed, which is the next phase of our research," said senior author Bryan Clary, M.D., chief of the Division of Hepatopancreatobiliary and Oncologic Surgery.

The study was published in Nature Chemical Biology online on Nov. 29.

Aptamers are small pieces of RNA that bind to a specific target molecule, usually a protein. They offer ease of use because they can be easily regenerated and modified and therefore have increased stability over some other agents, such as protein-based antibodies. Notably, they have a very low chance of immune-system interference（冲突，干涉）, making them great candidates for tumor diagnosis and therapy.

"Most importantly, it's not necessary to have detailed knowledge of protein changes in the disease before the selection process," said lead author Jing Mi, M.D., Ph.D., assistant professor in the Duke Department of Surgery. "This greatly simplifies the process of molecular probe development. The selected aptamers can be used to discover proteins not previously linked with the disease in question, which could speed up the search for effective therapies."

The researchers used a large pool of RNA strands and applied them to a rodent with a liver tumor, the type of metastatic tumor（转移瘤） that often results from a colon cancer（结肠癌） tumor.

"We hypothesized that the RNA molecules that bind to normal cellular elements would be filtered out（滤出，过滤）, and this happened," said Clary, who treats colon cancer patients. "In this way, we found the RNA molecules that went specifically to the tumor."

The researchers removed the tumor, extracted the specific RNA in the tumor, amplified these pieces of RNA to create a greater amount, and reinjected the molecules to learn which bound most tightly to the tumor. They repeated this process 14 times to find a good candidate.

The team found a tumor-targeting RNA aptamer that specifically bound to RNA helicase p68, a nuclear protein produced in colorectal tumors.