Scientists Reveal How a Single Molecule in the Body Can Drive Cancer Cells to Suicide Without Using Drugs
Scientists have revealed how a single molecule in the body triggers the body's tumor-destroying systems and a series of chain reactions that can kill cancer in a breakthrough discovery that could lead to the development of new drugs without the debilitating effects of traditional cancer therapies.
A team of researchers from Pennsylvania State University has identified a molecule called TIC10 that activates a protein that makes cancerous cells commit suicide, according to a new study published in the journal Science Translational Medicine.
The TIC10 molecule activates a protein called TRAIL (tumour-necrosis-factor-related apoptosis-inducing ligand), which suppresses the tumor development during immune surveillance, the immune system's process of identifying cancer cells in the body. Researchers said that this immune process is lost during cancer progression, which often leads to uncontrolled growth and spread of tumors.
Researchers emphasized that using TRAIL to combat cancer is essentially using the body's own defenses to fight the disease so it is not toxic to the body like chemotherapy or radiotherapy.
"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," lead researcher Wafik El-Deiry, an oncologist at Pennsylvania State University in Hershey, told Nature.
Experiments on mice showed that the TIC10 molecule significantly reduced a variety of tumors, including breast, lymphatic, colon and lung cancer. Researchers found that the molecule was particularly effective at triggering cell suicide in glioblastoma, a very difficult to treat brain tumor, after researchers found that glioblastomas mice treated with TIC10 in combination with cancer drug bevacizumab (Avastin) lived three times longer than untreated mice. Researchers added that even mice treated with TIC10 alone survived longer than those treated with the bevacizumab alone.
Previous studies on the TRAIL protein were not as successful as the latest study. Researchers said that the success of the latest study could be because of the small size of the TIC10, and that the molecule seems to make the body's healthy cells join in the fight against cancer cells. Researchers found that TIC10 doesn't just activate the TRAIL gene in cancerous cells, but also in healthy cells, in a process known as the "bystander effect" where cells near cancerous cells are also killed. The molecule also seems to stimulate nearby healthy cells to increase the amount of TRAIL receptors on their cell surface. Researchers explain that these receptors can then bind to the adjacent tumor cells to trigger their suicide.
While the latest experiments were done only done in mice, researchers believe that a similar approach would also work in humans.
"I was surprised and impressed that we were able to do this," El-Deiry said in a news release. "Using a small molecule to significantly boost and overcome limitations of the TRAIL pathway appears to be a promising way to address difficult to treat cancers using a safe mechanism already used in those with a normal effective immune system. This candidate new drug, a first-in-its-class, shows activity against a broad range of tumor types in mice and appears safe at this stage."