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Xiang (Shawn) Zhang, PhD
Professor, Department of Molecular and Cellular Biology
Lester and Sue Smith Breast Center
Baylor College of Medicine
Goal: To develop innovative strategies to eliminate circulating tumor cells and prevent metastasis.
Impact: Dr. Zhang is conducting laboratory studies to understand how immune cells enable tumor cell clusters to invade distant tissue and form new tumors. His research could lead to the identification of new immune approaches to target tumor cell clusters and prevent the spread of breast cancer.
What’s next: He and his team will continue their investigation into the ways in which clusters of circulating tumor cells (CTCs) – cells that are often found in the bloodstream of cancer patients – resist attack by immune cells, which allows them to spread more easily.
Circulating tumor cells (CTCs) are tumor cells that have broken away from the primary tumor and entered the circulation. They contain important clinical and biological information and can be used to monitor the tumor's response to therapy and the risk of metastasis. Dr. Zhang has observed that some CTCs travel as clusters as opposed to single cells, and that these clusters may be more efficient in colonizing distant organs and establishing metastases. Furthermore, his studies suggest that CTCs are at least partially dependent on the immune system. He and his team are now studying how these clusters form and how they could be targeted to provide new treatments that complement current immunotherapies for breast cancer.
Full Research Summary
Research area: Understanding how immune cells enable breast cancer tumor cell clusters to invade distant tissue and form new tumors.
Impact: Circulating tumor cells (CTCs) are cells that have broken away from the tumor and entered the circulation, which makes them detectable in a sample of blood called a liquid biopsy. CTCs are often found in the blood of cancer patients and indicate a poor prognosis. Research by Dr. Zhang and others has revealed that CTCs that travel in clusters are less vulnerable to attack by the immune system, allowing them to become established metastases. Dr. Zhang aims to discover why that is and ultimately use that knowledge to identify therapeutic strategies to block the spread of breast cancer.
Current investigation: He and his colleagues have been studying a type of immune cell called natural killer (NK) cells that are the primary immune cell that attacks CTCs. However, when CTCs are in clusters, NK cells are limited in their ability to destroy them. Dr. Zhang’s team will conduct laboratory studies to further understand how CTC clusters avoid natural killer cell surveillance and the mechanisms that both drive and support CTC cluster migration and formation of metastasis.
What he’s learned so far: Dr. Zhang studies have shown that NK cells are the primary immune cells that attack CTCs, but their effect is diminished when CTCs form clusters. This gives a selective advantage to CTC clusters over single CTCs to form metastasis and may explain the often-polyclonal nature of many metastatic breast tumors.
What’s next: In the coming year, his team will focus on epithelial-to-mesenchymal transition (EMT), a transformation of a tumor cell that is part of the intact tumor to one that can break away and travel. EMT is believed to be the primary mechanism of metastasis. Dr. Zhang’s team aims to understand the role of EMT on sensitivity to NK cell-mediated killing. The hope is that this research will lead to the development of new immunotherapies that are complementary to current treatments.
Dr. Zhang is an Associate tenured Professor at Lester and Sue Smith Breast Center of Baylor College of Medicine. He received his PhD degree from Columbia University under the mentorship of Dr. Lawrence Chasin where he focused on the biology of mRNA splicing. He then joined Dr. Joan Massague’s laboratory at Memorial Sloan Kettering Cancer Center, where he began to study cancer metastasis. He made several findings using an integrative strategy combining cancer genomics and experimental metastasis approaches. He was named McNair Scholar in 2011. He is also an awardee of the K99/R00 Pathways to Independence Grant from National Cancer Institute. At Baylor College of Medicine, Dr. Zhang continues to investigate biological mechanisms and therapeutic strategies of breast cancer metastasis. His long-term goals are to eradicate latent cancer cells in distant organs, and to reduce the incidence of overt-metastases.