Let the dormant cells continue to sleep, scientists try to understand the crouching cancer cells
July 4, 2018 Source: China Science News Author: Zonghua compilation
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Image source: Khuloud T. Al-Jamal & Izzat Suffian/Wellcome collection
For prostate cancer, tumors can shed cells elsewhere in the body.
After decades of designing drugs to kill rapidly dividing tumor cells, many cancer researchers are turning their way to targeting silent malignant cells that are dispersed in the body before they produce new tumors.
These cells catalyze the development of metastatic tumors, which are responsible for about 90% of cancer deaths. They are the source of the resurgence of heartbreaking cancer seen in many people. The seemingly successful initial treatment has given these people hope for their own cure. Therapies targeting targeted tumor cells often miss these silent cells because they are not actively dividing.
Dormant tumor cells are rare and difficult to screen out of trillions of common cells in the body. According to Julio Aguirre-Ghiso, a cancer researcher at the Icahn School of Medicine in Mount Sinai, New York, scientists have been lacking the tools to study them for many years. But all this is changing.
Recently, researchers gathered in Montreal, Canada. In Aguirre-Ghiso's view, this is the first meeting devoted to dormant cancer cells. “People realize that this is an important clinical need.â€
This need is especially necessary for cancers that have a high recurrence rate and sometimes relapse after years of treatment, such as breast, prostate and pancreatic cancer. "You cleared the tumor and received the radiation. You did this and did that, but sooner or later, the cancer will resurrect. Then, you said to yourself, 'Where did these things come from?'" Lawrence Berkeley, California Laboratory cancer researcher Mina Bissell said.
There is increasing evidence that dormant cells are separated from the maternal tumor early in development and pass through the blood vessels to new sites in the body. After "settling in" in other tissues or organs, the cells go to sleep and remain dormant until they are awakened by unknown triggers. Until then, they began to divide and form new tumors.
When cancer researchers tried to study this "crouch", they quickly encountered a problem: the cancer mouse model was designed to produce a fast-growing and highly lethal mother, or at least a tumor. However, researchers looking for "crouching" cells need slow-growing tumors. In this way, they have time to get rid of "malignant" cancer cells. Scientists also need the ability to track these cells long after they have been removed.
"This type of animal is hard to nurture," said Kathy Miller, a breast cancer expert at Indiana University. However, several laboratories have made progress and developed a model for tracking dormant cells in mice for more than one year.
The technique of identifying these cells is also important: cell biologist Joshua Snyder of Duke University School of Medicine uses a mixture of fluorescent markers to identify and track "malignant" cells that express cancer-associated genes. At the same time, at the meeting in Montreal, Jason Bielas, a geneticist at the Frederick Hutchinson Cancer Research Center in Seattle, Washington, showed the initial results of using a specific DNA sequence to label such cells with "barcodes." The researchers then used inexpensive DNA detection methods to identify these cells at a resolution of one billionth.
Once silenced cells are identified, new methods for judging which genes they express can help researchers determine the factors that induce dormancy and the triggers that awaken sleep cells. Miller said that with this information, it is possible to prevent cells from waking up. "Once these cells remain dormant, it won't cause my patient to die."
Efforts to keep sleep cells silent are also underway. In 2015, Aguirre-Ghiso Laboratories reported that the combination of two approved drugs, 5-azadeoxycytidine and retinoic acid, induced dormancy in prostate cancer cells grown in culture and mice. Now, oncologist William Oh, who is also working at the Icahn School of Medicine in Mount Sinai, and colleagues are convening prostate cancer patients to participate in a trial to test these findings clinically.
Others are looking for ways to kill dormant cells directly. Veronica Calvo-Vidal, a cancer researcher at the Aguirre-Ghiso lab, and colleagues collaborated with pharmaceutical companies to describe a protein inhibitor called PERK. It is expressed at abnormally high levels in dormant cancer cells. Early studies in mice have shown that this inhibitor kills cancer cells. Currently, the team is analyzing gene expression in individual dormant cells to better understand how inhibitors work.
However, Miller warns that it is equally important to develop a way to identify which cancers are most likely to relapse, because physicians can choose which patients have reason to accept such treatments. She and other oncologists who treat breast cancer have tried to determine which patients should receive further hormonal therapy to reduce the risk of tumor recurrence.
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