Cancer is most dangerous when it spreads from the primary tumor to other parts of the body. Responsible for about 90% of cancer deaths, metastasis is a grim reality of a complex process that scientists are still trying to understand.
Metastatic tumors develop years, sometimes decades, later in 30% to 40% of breast cancer survivors. Although treatments can lengthen the lives of women with recurrent or metastatic breast cancer, the disease is most often incurable at that point.
Scientists are now working to understand and detect early signs of breast cancer’s spread—and potentially prevent it.
“The question lurking in every survivor’s mind is, ‘Will my cancer come back?’” says cancer biologist Sandra McAllister, Ph.D., of Brigham and Women’s Hospital in Boston. “That’s what we’re trying to answer—what’s the likelihood the cancer will come back and how do we target it before it does.”
Using a four-year, $720,000 grant from the American Cancer Society, McAllister is building on her previous research that found some tumors release substances that awaken dormant cancer cells elsewhere in the body. These malignant offspring had broken away from the primary tumor before its removal and landed quietly in a tissue far from the original mass that spawned them. Once awakened, the cancer cells turn into life-threatening metastatic tumors.
McAllister and her lab team gave this long-range communication a name: systemic instigation. It is an “instigator” tumor that signals dormant “responder” cancer cells to grow.
McAllister is now trying to figure out what specific characteristics make a tumor an instigator. “Two different tumors may grow at the same rate and look the same under the microscope, but one acts like an instigator and the other one doesn’t,” she says.
To study this, she is implanting two kinds of tumors into mice: breast tumor tissue from patients who had a lumpectomy or mastectomy, and known “responder” tumors. If the responder cells come to life, McAllister’s team dubs the test sample an instigator and molecularly picks it apart along with whatever proteins, growth factors and bone marrow cells are found circulating in the blood. They are conducting similar experiments to learn what makes responder cancer cells susceptible to an instigating tumor’s tricks.
“Our goal is to learn exactly what makes an instigator an instigator so that we can look at a tumor specimen or a blood sample and predict whether it’s likely to cause systemic instigation,” McAllister says. Her earlier research found that some instigating tumors release a protein called osteopontin, and she’s now discovered blood-clotting platelets can instigate cancer growth as well.
McAllister anticipates one day a test will allow oncologists to determine whether a breast cancer patient’s tumor is an instigator and thus likely to recur, helping guide treatment decisions.
She also envisions the development of targeted drugs that would cut the lines of communication between instigating and responding breast cancer cells. “We could halt the systemic instigation process because we would know what to target,” McAllister says. “Once we finish identifying the problem, we can start coming up with the solutions.”
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