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Kornelia Polyak, MD, PhD


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Kornelia Polyak, MD, PhD


  • Professor of Medicine, Harvard Medical School

Contact Information

  • Office Phone Number617-632-2106
  • Fax617-580-8490


Dr. Polyak obtained her M.D. degree in 1991 from the Albert Szent-Györgyi Medical School in Szeged Hungary and her Ph.D. degree in 1995 from Cornell University Graduate School of Medical Sciences/Sloan-Kettering Cancer Center, New York. Dr. Polyak completed her postdoctoral training in Baltimore at the Johns Hopkins Oncology Center in the laboratory of Drs. Bert Vogelstein and Ken Kinzler. Dr. Polyak joined the faculty of Dana-Farber Cancer Institute and Harvard Medical School in 1998 as Assistant Professor of Medicine and was promoted to Professor in 2011. Dr. Polyak’s laboratory is dedicated to the molecular analysis of human breast cancer with the goal improving the clinical management of breast cancer patients. Her lab has devoted much effort to develop new ways to study tumors as a whole and to apply interdisciplinary approaches. Using these methods Dr. Polyak’s lab has been at the forefront of studies analyzing purified cell populations from normal and neoplastic human breast tissue at genomic scale and in situ at single cell level and to apply mathematical and ecological models for the better understanding of breast tumor evolution. She has also been successful with the clinical translation of her findings including the testing of efficacy of JAK2 and BET bromodomain inhibitors for the treatment of triple-negative breast cancer in clinical trials. Dr. Polyak have received numerous awards including the Paul Marks Prize for Cancer Research in 2011, the 2012 AACR Outstanding Investigator Award for Breast Cancer Research, and the Rosalind Franklin Award in 2016. She is also a 2015 recipient of the NCI Outstanding Investigator award.

Recent Awards:

  • 14th Rosalind E. Franklin Award for Women in Science, NIH, 2016
  • Outstanding Investigator Award, NCI 2015
  • AACR Outstanding Investigator Award for Breast Cancer Research, San Antonio, TX 2012
  • Paul Marks Award for Cancer Research, Sloan-Kettering Cancer Center, New York, NY 2011
  • Elected to the Johns Hopkins Society of Scholars 2008
  • 27th Annual Award for Outstanding Achievement in Cancer Research, American Association for Cancer Research 2007
  • Claire W. and Richard P. Morse Research Award, Dana-Farber Cancer Institute 2006
  • Tisch Family Outstanding Achievement Award, Dana-Farber Cancer Institute 2005
  • V Foundation Scholar Award 2001
  • Sidney Kimmel Scholar Award 1999


Molecular Basis of Breast Tumor Evolution
Research in my laboratory is dedicated to the molecular analysis of human breast cancer. Our goal is to identify differences between normal and cancerous breast tissue, determine their consequences, and use this information to improve the clinical management of breast cancer patients. The three main areas of our interests are: (1) how to accurately predict breast cancer risk and prevent breast cancer initiation or progression from in situ to invasive disease, (2) better understand drivers of tumor evolution with special emphasis on metastatic progression and therapeutic resistance, and (3) novel therapeutic targets in breast cancer with particular focus on “bad” cancers such as triple-negative breast cancer and inflammatory breast cancer. All of our studies start with analyzing samples from breast cancer patients (or normal healthy women for the risk studies), formulate hypotheses based on our observations, use experimental models to test these, and then translate back our findings into clinical care.
Highlights from our breast cancer risk and prevention study: The highest impact on breast cancer-associated morbidity and mortality will be achieved with two tools.  The first tool is a test that accurately predicts an individual’s risk of developing breast cancer. This will allow us to identify who needs preventive action and who does not.  Second, is to discover the best agent for prevention that will be universally effective.  We know that inheriting mutated BRCA1 and BRCA2 genes confer a high risk of breast cancer, and the most effective prevention strategy currently available is prophylactic oophorectomy and mastectomy. Other significant determinants of breast cancer risk are reproductive history and mammographic density. Epidemiological data suggest that pregnancy induces long-lasting effects in the normal breast, except in BRCA1 and BRCA2 mutation carriers, where pregnancy does not decrease breast cancer risk.
What cells need to be eliminated in the breast to reduce risk?  A number of studies have shown that breast epithelial progenitor cells are likely the “cell-of-origin” of breast cancer. It stands to reason then, that eliminating them will abolish tumor development. In recent work we analyzed and characterized multiple cell types from normal breast tissues of nulliparous and parous women, including BRCA1 and BRCA2 mutation carriers. We detected the most significant differences in breast epithelial progenitors and found that the frequency of these cells is higher in women with higher risk of breast cancer. We have also identified key signaling pathways important for their proliferation and showed that by modulating the activity of these pathways we can decrease the frequency of the progenitor cells, thus, potentially reducing breast cancer risk. We propose that the progenitor markers identified can be used for breast cancer risk prediction and that depleting these progenitors will decrease the risk of breast cancer. We are pursuing these studies in large cohorts in women and in rodent models of breast cancer (prevention) with immediate plans to translate our findings to high risk women as the drugs used to deplete these progenitors are already in clinical trials for cancer treatment.
Highlights from our cancer heterogeneity studies: With rare exceptions tumors are thought to originate from a single cell. Yet, at the time of diagnosis the majority of human tumors display startling heterogeneity in many structural and physiological features, such as cell size, shape, metastatic proclivity, and sensitivity to therapy. This diversity within tumors (intratumor) complicates the study and treatment of cancer because small tumor samples may not be representative of the whole tumor and because a treatment that targets one tumor cell population, may not affect another, leading to a poor clinical response. On the positive side, intratumor diversity is a type of “looking glass” for a particular cancer from which we can both learn its past and predict its future.
Until recently, mainstream cancer research has been focusing on the identification and therapeutic targeting of “cancer-driving” genetic alterations.  However, recent large-scale sequencing of breast cancer genomes has been disappointing and identified relatively few recurrent mutations that could be explored for therapy. In addition, most of the mutations were detected only in a subset of tumors and at a low frequency, making it difficult to determine their relevance in tumorigenesis. The outcome of these sequencing studies reinforced the already high interest in intratumor heterogeneity. Intratumor heterogeneity for heritable traits is a fundamental challenge in breast cancer, underlying disease progression and treatment resistance. Yet our understanding of its mechanisms, and as a consequence, our ability to control it remains limited. This is largely due to the cancer-gene and cancer cell-focus of mainstream cancer research and the reliance on experimental models that poorly reproduce this key aspect of the human disease.
We have developed a model of intratumor clonal (i.e., group of cells with common ancestry) heterogeneity in breast cancer and utilized this to assess the functional relevance of clonal interactions in metastatic progression. We found that polyclonal tumors were commonly metastatic, even though none of the individual clones present in them showed this behavior in monoclonal tumors. We have also analyzed breast tumor samples before and after pre-operative chemotherapy, or at different stages of disease progression (i.e., primary and metastatic lesions) for the degree of intratumor genetic and phenotypic heterogeneity at the single cell level. We found that tumors with the lowest pretreatment genetic diversity responded the best to treatment and that distant metastatic lesions had higher genetic diversity compared to primary tumors and lymph node metastases. Lastly, we have developed mathematical models based on these experimental data that can infer the evolution of tumors during treatment. Based on these data, we hypothesize that intratumor heterogeneity per se is a driver of metastatic spread and therapeutic resistance. Thus, measures of intratumor heterogeneity can be used to predict the risk of metastasis and to personalize therapy based on this. At the same time, understanding of how heterogeneity within tumors promotes disease progression may reveal new therapeutic targets and would allow us to design more effective and individualized treatment strategies.


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