The STING protein, which activates immunity, prevents lung cancer from causing metastases, according to a research led by Joan Massagué that is presented today in the journal Nature.
Several pharmaceutical companies are developing drugs that act like the STING protein. But, in clinical trials conducted so far, these drugs have been given to people whose metastases were already progressing. Massagué's research indicates that these drugs would be more effective if they were administered earlier, when the metastases have not yet manifested.
The Catalan researcher, director of the Sloan Kettering Institute for cancer research in New York, has successfully tested this strategy in mice with lung cancer. The results of the research open the way to testing it in people as well.
Although the experiments have been carried out in animals with lung adenocarcinoma - the most common type of lung cancer - the same strategy may be effective in other types of cancer. "We have obtained similar results in triple-negative breast cancer, the other type of tumor that we have studied," reports Massagué. "If we go two to zero, it means that this discovery will probably be important in other cancers."
The advance is based on increasingly detailed scientific understanding of how metastases occur. According to research carried out by Massagué himself and other scientists, it is common for tumor cells to remain disseminated in different organs after a person has been treated for cancer and is apparently cured.
These cells can remain for years in a quiescent state, without multiplying and without being detected by the immune system. If one day they are activated, which does not happen in all cases, that is when the metastases grow.
The strategy proposed by Massagué consists of eliminating these cells when they are asleep, in a quiescent state, so that they can never cause metastasis again.
According to the results presented in Nature, tumor cells inhibit the STING protein when they enter a quiescent state, which allows them to hide from the immune system. This protein, whose name corresponds to the initials in English of interferon (IN) gene (G) stimulator (ST), activates multiple molecules of the immune system, including some interferons. This in turn activates immune cells such as T lymphocytes and NK (Natural Killer) cells, which have the ability to kill quiescent tumor cells.
In experiments carried out with two different experimental drugs that act like STING, tumor cells disseminated in different organs of mice with lung cancer have been eliminated and the growth of metastases has thus been prevented.
The application of these results to people will not be immediate, warns Massagué. “With a new drug with potential against metastasis, it is first tested in patients who no longer respond to standard treatment; if the results are positive, then it is tried combining it with the standard treatment; and if the results are positive again, then it can be tested in patients who have had cancer and have not yet developed metastases”, explains the researcher. “Although it seems like a very slow path, we must remember that STING as a biological mechanism was discovered just ten years ago. Ten years ago the only known Sting was a musician.
