Jeroen Roose, Ph.D., Principal Investigator, and Hugo Gonzalez Velozo, Ph.D., Postdoctoral Fellow at UC San Francisco. This video talks about their study “Cellular architecture of human brain metastases,” which is a single-cell analysis of huma BrM that reveals multiple conserved features across multiple cancer and points the way to potential future improvements in immune therapies. With thanks to Joanna Phillips, MD, Ph.D., and Matthew Spitzer, Ph.D., who collaborated with Dr. Gonzalez Velozo. All this could not be possible without the late Zena Werb, Ph.D., for starting this with her visions for the future treatment.
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“What we haven’t looked at adequately is what keeps a cell in a non-cancer state. By 2050, I believe scientists will be addressing the neighborhood, or microenvironment, around a tumor and better understanding its role in keeping cancer cells under wraps.”
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Their greatest hope for 2050?
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“That our treatment goals for many more cancers will have shifted from eradication to managing these diseases as long-term conditions, like arthritis. In other words, we’ll die with it, not from it.”
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UC San Francisco researchers discovered two functional archetypes of metastatic cells spanning seven different types of brain cancers, each having both immune and non-immune cell types, using data from over 100,000 malignant and non-malignant cells from 15 human brain metastases. Their findings, which were published in the Feb. 17 issue of CELL, present a potential roadmap for metastatic tumor growth that might be exploited to develop medicines to help patients with metastases.
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The UCSF researchers investigated metastatic tumor cells (MTCs) and discovered eight functional processes expressed by MTCs across seven forms of metastatic brain cancer, lead by first author Hugo Gonzalez, PhD, and senior authors Jeroen Roose, PhD, and the late Zena Werb, PhD. These specialized and complementary processes operate together within single cells to build two recurrent cell archetypes, one inflammatory and the other proliferative, that co-exist within each metastatic tumor and are both shaped by immune cells, according to the researchers.
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The most prevalent type of brain cancer is brain metastasis, which occurs roughly ten times more frequently than cancer that starts in the brain. While brain metastasis therapy options have improved in recent years, there is still much to learn about metastasis genesis.
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To uncover and comprehend the recurrent patterns that characterize the process of metastasis formation in patients, the researchers coupled high-dimensional single-cell analysis of human brain tissue metastases from various cancer types with experimental models. They also discovered a similar metastatic niche or microenvironment, as well as an immunosuppressive stroma enriched in T-cells and metastasis-associated macrophages, which appear to be important in the dynamics of the two archetypes.
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Werb, a world-renowned cancer biologist and associate director for basic science at the University of California, San Francisco’s Helen Diller Family Comprehensive Cancer Center, revolutionized the field by emphasizing the importance of cells’ local “neighborhoods” in determining tumor growth and behavior. Her work paved the way for immunotherapy and other current methods to cancer treatment over the span of four decades. Werb died in 2020 at the age of 75, but her coworkers, for whom she was a mentor, continue to carry on her legacy.
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Gonzalez’s study, according to Roose, laid a solid foundation for the team’s collaboration with the UCSF Endeavor initiative, which aims to better understand how cancer cells interact with the host cells that surround the tumor to cause metastases.