Cancer researchers have found a molecule that initiates the body's system that promotes cell death of cancer tissues, by triggering the body's tumor destroying system. The molecule known as TIC10, is described as a potent, orally active and stable small molecule. The molecule was found to activate a part of the immune system known as TRAIL (tumor-necrosis-factor-related apoptosis-inducing ligand).
"TRAIL is a part of our immune system: all of us with functional immune systems use this molecule to keep tumors from forming or spreading, so boosting this will not be as toxic as chemotherapy," says Wafik El-Deiry, an oncologist at Pennsylvania State University in Hershey, PA. El-Deiry is also the author of the study, which is published in the journal, Science Translational Medicine on Feb. 7.
The experiments were conducted on mice and showed that TIC10 had worked was effective with a variety of tumors, including breast, lymphatic, colon and lung cancer. When the molecule was given to mice with glioblastoma, the molecule was found effective at triggering cell suicide. Glioblastoma is stubborn and known to be difficult to treat, a combination TIC10 and another tumor treating drug, bevacuzumab was also administered to the mice. It was found that the mice survived three times longer as the untreated mice. Researchers found a 6% increase in survival rate even among the mice that were treated with just the TIC10 drug.
"We didn't actually anticipate that this molecule would be able to treat brain tumors - that was a pleasant surprise," said El-Deiry. He explained that TIC10 is smaller than proteins and the compact size makes it able to cross the blood brain barrier that separate the brain from the circulatory system. The protective barrier would often block anti-cancer drugs while it was serving the normal function of blocking other hazards from infecting the brain, such as microbes. TIC10 was also found activate TRIAL in the healthy cells in addition to the cancerous ones. It acts to stimulate the healthy cells to increase more TRAIL receptors, resulting in the receptors binding to the cancer cells and triggering the kill process.
The research team is confident that a similar approach to cancer cell treatment using TIC10 would work on humans even though the study was conducted using mice. "TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRIAL," said the report.
Some researchers remain skeptical due to their experience with the failure of TRAIL based strategies. During the mid 1990's, many clinical trials conducted using TRAIL based therapies were not very successful in treating cancer. Large biomedical groups shelved their TRIAL based drugs due to the ineffective results of the previous trials.
