Metastasis occurs when cancer cells leave the original tumor and move through the blood or lymphatic systems to other parts of the body. Scientists had initially assumed that metastases would contain cells that were the same as those in the primary tumor. Studies suggested this was not necessarily the case. Now, new technologies are allowing researchers to learn even more about how metastases differ from primary tumors.


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Genomic sequencing of cancer cells can identify the mutations that help a tumor grow. Oncologists routinely use genetic information found in the primary tumor to determine treatment options. For example, lung cancer with an EGFR mutation can be treated with Tarceva (erlotinib), while melanoma with a BRAF mutation can be treated with a number of different targeted drugs. However, it is rare for oncologists to perform genomic sequencing on cells obtained from metastases. “As a result, it was a complete black hole for research,” says Jesse Boehm, a cancer researcher at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts.

To learn more, researchers from the Broad Institute and the Dana-Farber Cancer Institute in Boston used genomic sequencing to compare primary tumors and metastases in 44 breast cancer patients. The results, reported at the 2016 San Antonio Breast Cancer Symposium, showed that the metastases more frequently had mutations in multiple genes.

Other recent studies have pointed to distinct genetic differences between primary tumors and metastatic tissue in a variety of cancer types, including colorectal and pancreatic cancer.

From the outset, tumors tend to be made up of a diverse group of cells. Metastatic cancer cells may be genomically different from the primary tumor, says Boehm, because the initial treatments may have killed most of the tumor, but left behind a small group of cells with a profile that allowed them to survive.

“If we can understand [how the mutations help] make the tumor resistant to therapy,” we could “potentially identify ways to treat these tumors [with targeted drugs] or overcome the resistance that occurs in them,” says Nikhil Wagle, an oncologist at the Center for Cancer Precision Medicine at Dana-Farber who was involved in the study.

A new type of blood test called a liquid biopsy allows researchers to analyze cancer cells the tumor sheds into the bloodstream. Wagle says that liquid biopsies will make it easier to compare metastases with primary tumors. In the future, liquid biopsies may also make it easier for oncologists to learn whether the metastasis has a mutation that can be targeted with drugs that are approved for other types of cancer or that are in clinical trials.

The knowledge that tumors can change when they metastasize is already playing a role in cancer care. For example, in breast cancer patients, metastases may be biopsied to see if a cancer that was HER2-positive has become HER2-negative. The biopsy allows the doctor to determine whether the tumor can still be treated with a HER2-targeted drug.

“To understand tumor evolution and resistance to therapies, you really do need to re-biopsy patients after their cancer metastasizes,” Wagle says.