Daniel A. Haber, MD, PhD

Massachusetts General Hospital
Boston, Massachusetts

Titles and Affiliations

Director, Massachusetts General Hospital Cancer Center
Kurt J. Isselbacher Professor of Oncology
Harvard Medical School
Investigator, Howard Hughes Medical Institute
Massachusetts General Hospital
Boston, Massachusetts

Research area

To understand how circulating tumor cells in the blood of breast cancer patients give rise to metastases.

Impact

Metastasis is the primary cause of breast cancer deaths, but how metastatic tumors develop is not well understood. Dr. Haber and his team study rare tumor cells, called circulating tumor cells (CTCs), that escape from the primary cancer and travel in the bloodstream to distant organs. There, they can grow and develop metastases. Dr. Haber’s lab bioengineered microfluidic devices, which isolate CTCs from patients’ blood, and the team is currently growing these cells in the laboratory to learn more about them, and consequently learn more about the metastatic process. Dr. Haber’s ultimate goal is to identify therapeutic strategies to target CTCs and stop the metastatic spread of cancer cells from early breast cancers, as well as prevent the further spread of breast cancer that has already metastasized.

Progress Thus Far

Through molecular analysis of CTCs in the laboratory, the team discovered a new vulnerability in cancer cells: because tumor cells divide rapidly, this exerts unique stresses on the cells. Dr. Haber and his team identified a biological pathway that tumor cells need to adapt to these stresses. Disrupting this pathway could therefore present a new therapeutic opportunity. In addition to these studies, the team also continues to develop innovative devices for capturing CTCs. They developed a new device capable of analyzing larger amounts of blood compared to current methods, increasing the number of CTCs from 1-10 to thousands from a single sample. permitting detailed molecular analysis. This innovative device represents a potential opportunity to replace invasive biopsies of breast cancer with a less invasive blood-based approach.

What’s Next

Using their new technique for CTC isolation, the team hopes to test its use for clinical applications. They also plan to continue their laboratory studies by analyzing how tumor cells develop resistance to next generation hormone therapies. These insights will help guide future therapeutic strategies in advanced refractory breast cancer.

BCRF funding has been exceptionally impactful for our lab, making it possible for us to dedicate resources to the study of advanced, treatment-resistant breast cancer, and to tackle research questions that are ‘risky’ but have potentially high impact.

Biography

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.