Wherever it may begin, cancer often spreads to other organs and parts of the body through a process called metastasis, which, if left unchecked, can be fatal. A new paper, from scientists at the Spanish National Cancer Research Center (CNIO) and Weill Cornell Medicine, is looking at the current state of metastasis research, to help scientists cripple cancer's ability to spread throughout the body.

Cancer wouldn't be nearly as crafty a foe if it stayed put, but even if doctors are able to kill the primary tumor, others can turn up in different parts of the body thanks to metastasis. Past breakthroughs in that area include identifying a key protein responsible for cancer cells' ability to travel, and a pair of proteins that help protect those cells on their journey.

While scientists don't fully understand the process, it is known that before cancer cells spread to the new site, the tumors will begin to put in some ground work to help them survive and grow there. That takes the form of fluids and abnormal cells secreted by the primary tumor, to begin altering the new site to allow the cancer cells to take hold and thrive there – essentially, laying a foundation for itself. Those foundations are called "pre-metastatic niches," and being able to identify these areas in advance could help doctors get a head start to stop cancer's spread and improve the survival rates of patients.

"Emerging evidence from our laboratory and others identified pre-metastatic niches in patients with various cancers," says David Lyden, an author of the paper. "This is a paradigm shift in our understanding of metastasis that will be the cornerstone for developing strategies for the preventive treatment of metastasis, rather than treating metastasis after the fact."

The paper points out three main processes that take place in an organ before cancer cells metastasize there, all of which could be used as markers to indicate when and where tumors will spread. Inflammation, which indicates that the immune cells have been infiltrated; leaky blood vessels; and signs that the organ is beginning to be "remodeled," are all possible signs that emerging imaging techniques could search for.

"A better understanding of the biology underlying the inflammation and blood vessel dysfunction in pre-metastatic niches will allow us to identify therapies to block metastatic progression," says Haiying Zhang, co-author of the paper.

The red areas indicate breast cancer metastatic cells beginning to form in pre-metastatic niches in lung tissue(Credit: Héctor Peinado/CNIO)

Knowing is half the battle, but what can we do about it then? The paper outlines several methods on blocking metastasis that are currently being explored, including disrupting the primary tumor's signals, inducing a dormant state in the pre-metastatic niches, or finding ways to restart the immune response at the new site to fight off the invading cancer cells before they take hold.

The paper concludes that targeting cancer at pre-metastatic niches is a technique with plenty of potential, but there's still a lot of work to do in the field in order to translate the concept "from bench to bedside."

"The more we move forward in the early detection of metastasis, the higher the survival rates will be," says Héctor Peinado, an author of the paper. "If we can predict that a tumor is going to metastasize and detect where, and we can stop it in that time window, it will be easier to treat cancer."

The paper was published in the journal Nature Reviews.

Source: CNIO

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