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Daniel A. Haber, MD, PhD
Director, Massachusetts General Hospital Cancer Center
Kurt J. Isselbacher Professor of Oncology
Harvard Medical School
Investigator, Howard Hughes Medical Institute
Massachusetts General Hospital
Goal: To understand how circulating tumor cells in the blood of breast cancer patients give rise to metastases.
Impact: Dr. Haber is studying circulating tumor cells (CTCs) – cells that have broken away from the tumor and entered the circulation. These are often specialized cells that settle in distant tissues and give rise to metastases (the spread of breast cancer to distant sites). His goal is to identify and target the vulnerabilities in CTCs to suppress the metastatic recurrence of breast cancer.
What’s next: He and his team will continue to characterize the properties of CTCs derived from the blood of breast cancer patients, to understand their ability to give rise to metastatic lesions.
Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and travel through the lymphatic and blood circulation. This allows them to invade other tissues in the body and form new tumors – a process called metastasis. Dr. Haber is studying these cells to determine what makes them able to survive in the bloodstream when most breast cancer cells do not. He has developed new technologies to isolate and analyze CTCs from the blood to determine how they produce metastases.
Full Research Summary
Research area: Characterizing circulating tumor cells to determine their role in metastasis and to devise strategies that target them to prevent the spread of breast cancer.
Impact: Metastasis is the primary cause of breast cancer deaths, but early events in metastasis are not well understood. Dr. Haber is studying rare cancer cells called circulating tumor cells (CTCs), which travel in the blood—something most cancer cells are unable to do—and settle in distant tissues such as the lung, bone, liver, or brain. He is employing a novel technology to isolate CTCs from the blood as a potential non-invasive way of monitoring breast cancer during treatment or for early detection of invasive cancers. His team hopes to develop strategies to prevent the metastatic spread of cancer cells from primary breast cancer as well as prevent the further spread of breast cancer that has already metastasized.
Current investigation: He and his colleagues have been using liquid biology to isolate and culture CTCs in the laboratory to study their properties and vulnerabilities, and ultimately develop novel strategies to suppress breast cancer metastasis.
What he’s learned so far: Dr. Haber and his team have engineered a device that can sort out CTCs from large amounts of cells in the blood of breast cancer patients. This has enabled the isolation of large quantities of CTCs for characterization. They have also developed cell lines from isolated CTCs and shown that the CTCs are highly tumorigenic in laboratory models. Investigations to identify the genes that would enhance metastasis showed that genes involved in protein translation (including a structural ribosomal protein RPL15) were repeatedly enriched in those CTCs associated with metastases. In fact, overexpression of RPL15 in multiple cultured CTCs demonstrated a dramatic increase in their metastatic potential. These results indicate that a subset of breast cancer CTCs, characterized by high ribosomal protein content may constitute a high-risk population with increased metastatic potential and that may be vulnerable to inhibitors of protein translation.
What’s next: He and his team will continue to analyze CTCs derived from blood specimens of women with breast cancer and decipher cellular pathways that allow them to produce metastases. They will also test how their new technology for isolating large volumes of CTCs can be applied to the study of breast cancer – having access to large quantities of cells to test the presence of the estrogen receptor or HER2 (i.e., targets of breast cancer therapy) would help to identify patients who may benefit from subsequent treatment.
Dr. Haber is Director of the Massachusetts General Hospital Cancer Center and the Kurt J. Isselbacher Professor of Oncology at Harvard Medical School. His laboratory interests have focused on the area of cancer genetics, including the etiology of the pediatric kidney cancer Wilms tumor, genetic predisposition to breast cancer, and targeted cancer therapies. His laboratory reported that lung cancers with activating mutations in the epidermal growth factor receptor (EGFR) are uniquely sensitive to tyrosine kinase inhibitors that target this receptor. This observation has had important implications for the genotype-directed treatment of non-small cell lung cancer, and more broadly for strategies to identify critical genetic lesions in cancers that may serve as an "Achilles heel" and be suitable for molecular targeting. In collaboration with Dr. Mehmet Toner’s laboratory, Dr. Haber’s laboratory has recently established the application of a novel microfluidic technology for quantifying and purifying Circulating Tumor Cells (CTCs) from the blood of patients with various epithelial cancers. This new application has potentially profound implications for early diagnosis of cancer and for noninvasive molecular profiling of cancers during the course of therapy. Building on his early studies in breast cancer that characterized contributions of founder mutations in BRCA1 and CHEK2 to early onset breast cancer, Dr. Haber’s most recent work has applied digital RNA profiles of breast CTCs for pharmacodynamic monitoring of estrogen receptor signaling following therapy, and the generation of ex vivo breast CTC cultures to define functional properties of these metastatic precursor cells.
Dr. Haber received his MD and PhD degrees at Stanford in 1983, completed an internal medicine residency at MGH, clinical oncology training at the Dana-Farber Cancer Institute, and a postdoctoral research fellowship at MIT. He joined the faculty of Harvard Medical School in 1991. Dr. Haber’s numerous awards include a MERIT Award from the National Cancer Institute, the Doris Duke Distinguished Clinical Scientist Award, and a Dream Team Award from Stand Up To Cancer. He received the Richard and Hinda Rosenthal Memorial Award from the American Association for Cancer Research (AACR). He was appointed to the Howard Hughes Medical Institute in 2008 and elected to the Institute of Medicine/National Academy of Medicine in 2009, the American Academy of Arts and Sciences in 2011, the National Academy of Sciences in 2018, and as a Fellow of the AACR Academy in 2019.