Scientists have arrived at a key understanding about how cancers in individual patients spread, or metastasize, a study from the Stanford University School of Medicine and other collaborating institutions reports.

The study found that mutations that drive cancer growth are common among metastases in a single patient.

Most cancer-related deaths are caused by metastases, or secondary tumors in distant locations of the body that have spread away from the original, primary tumor. While primary tumors can often be surgically removed, metastatic tumors typically require treatment, such as standard chemotherapy or targeted therapy. The success of such new targeted therapies depends on the presence of a specific mutation in all cancer cells, in particular in metastatic tumors.

Until now, most studies that aimed to decode the genetic variability, or heterogeneity, of cancers focused mainly on primary tumors. And while that information is still extremely valuable, it leaves much of the story untold; cancer cells are notorious for their ability to change, evolve, and evade treatments, particularly as they spread in the body.

“We took samples from multiple untreated metastases of each patient, and we observed a mix of overlapping and differing driver mutations,” said Johannes Reiter, PhD, an instructor of radiology at Stanford. “But through computational analyses, we inferred that the driver mutations that were most likely to contribute to cancer development were shared among all metastases in each patient.”

A tumor comprised of billions of cells is riddled with genetic mutations; cancer cells and normal cells acquire multiple mutations as they divide. Identifying the driver mutations that significantly contribute to cancer development is critical to precision oncology, in which doctors aim to treat a patient’s cancer based on its genetic composition.

“Doctors might take a sample of the primary tumor and find some mutation—call it mutation X—in a driver gene and then treat it with a drug that targets that driver gene to specifically kill all cells that have mutation X,” Reiter said. “But what if that particular mutation is only present in some of the metastases of the patient?” Only the metastases comprised of cells with mutation X would respond to treatment and shrink or go extinct; those without mutation X would continue to grow. In the end, the doctor wouldn’t see a remission of the patient’s cancer if driver mutations were different across its metastases. “So that’s why it’s very important for us to know whether or not the driver gene mutations are the same across all metastases of the patient,” Reiter said.

The paper was published September 7 in Science. Reiter; postdoctoral scholar Alvin Makohon-Moore, PhD, at Memorial Sloan Kettering Cancer Center; and graduate student Jeffrey Gerold, at Harvard University, share lead authorship. Martin Nowak, PhD, professor of biology and of mathematics at Harvard University, is the senior author.