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Andrea Lim, a fifth-year molecular and cellular biology graduate student at Fred Hutchinson Cancer Research Center and the University of Washington, recently won a National Cancer Institute Predoctoral to Postdoctoral Fellow Transition Award.
The award seeks outstanding graduate students with the potential for pursuing a career as an independent cancer researcher. The award provides up to six years of support for graduate students through the process of finishing their doctoral dissertations (one to two years) and continued through their transition to mentored postdoctoral research training (up to four years).
Lim, who is working on her doctoral dissertation proposal, investigates the mechanisms of disseminated tumor cell, or DTC, quiescence (or dormancy) regulation by the lymph node microenvironment. DTCs are thought to be responsible for metastasis, or cancer spread, which can lead to cancer-related deaths.
Lymph nodes are the most common site of metastasis for breast cancer, and results from clinical research studies suggest that disseminated tumor cells in the lymph nodes contribute to the reappearance of malignant disease.
“A big question we’d eventually like to answer is: Is there an advantage for a breast tumor cell to go through a lymph node on its way to another site? Or is it better to go exclusively through the blood?” said Lim’s mentor, Dr. Cyrus Ghajar, director of the Laboratory for the Study of Metastatic Microenvironments at Fred Hutch. “Andrea’s research takes the first steps toward answering that question, because she is uncovering what regulates breast tumor cells once they arrive into lymph nodes … and she is also developing methods to track cells within the lymph node so that we can potentially account for them once they leave and go to other organs.”
Lim's overall goal is to identify lymph node-specific therapeutic targets to mitigate delayed relapse in breast and other cancers.
“I think it’s really fascinating that this cascade of events occurs not just in the cell that has lost control of its normal function, but to the cells around it, how are they responding, and then how this actually presents in the patient,” she said. “These are all really rich areas that need to be studied.”
For Lim’s postdoctoral research, she hopes to investigate how the act of dissemination itself influences tumor cells, specifically looking at different pressures cancer cells can experience in their journey from the primary tumor to the secondary site, as well as looking to see if these different experiences affect metastatic success.
“Since we know that the microenvironment greatly influences tumor-cell behavior, it's intriguing to think that we might be able to predict which DTC population contributes to metastasis and focus on eliminating those cells,” she said.
Lim hopes the results of her proposed studies will draw attention to the selective nature of cancer-cell dissemination and shed light onto mechanisms that allow DTCs to escape the immune system, such as co-opting the lymph node’s ability to eliminate self-recognizing T cells, resulting in a more tolerant environment toward DTCs.
“Most of the work done on metastasis has focused on tumor cells that disseminate through the blood to vital organs, but DTCs aren't a static population and we now have evidence of what physicians and scientists have long believed: that DTCs can traffic to lymph nodes and then continue on to seed other sites,” Lim said. “So discounting lymph node DTCs as not contributing to disease is a mistake, and it's encouraging that the NCI is interested in studying this population of tumor cells. Hopefully, the projects I proposed will contribute to our understanding of how they impact disease.”
Lim is the first person at the Hutch to receive this prestigious award.
“Andrea has thought deeply about her project, works hard at it, is not easily deterred, and is a very talented writer,” Ghajar said. “I think these qualities shine through.”
