Kornelia Polyak, MD, PhD

Kornelia Polyak, MD, PhD

Researcher

Contact Information

Office Phone Number

617-632-2106

Fax

617-580-8490

Biography

Kornelia Polyak, MD, PhD

Kornelia Polyak, MD, PhD, is a Professor of Medicine at Dana-Farber Cancer Institute, Harvard Medical School, and a co-leader of the Dana-Farber Harvard Cancer Center Cancer Cell Biology Program.  Dr. Polyak is an internationally recognized leader of breast cancer research.  Her laboratory is dedicated to improving the clinical management of breast cancer patients by understanding molecular and cellular determinants of breast cancer risk and tumor evolution.  Dr. Polyak has devoted much effort to develop new ways to study tumors and to apply interdisciplinary approaches.  Dr. Polyak has received numerous awards including the Paul Marks Prize for Cancer Research, AACR Outstanding Investigator Award for Breast Cancer Research, and the 14th Rosalind E. Franklin Award for Women in Science.  She is a recipient of the NCI Outstanding Investigator award (2015 and 2022) and received a Distinguished Alumna Award from Weil-Cornell in 2020.  Dr. Polyak was the American Association for the Advancement of Science Fellow in 2019, member of the Fellows of the AACR Academy in 2020, and to the National Academy of Sciences and the National Academy of Medicine in 2022.  She was also a recipient of the American Cancer Society Research Professor Award in 2022 and received the 2023 AAACR Distinguished Lectureship in Breast Cancer Research award.

Researcher

Physician

Professor of Medicine, Harvard Medical School

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

Research

    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.

    Publications

      • Heterogeneity and transcriptional drivers of triple-negative breast cancer. Cell Rep. 2023 Dec 26; 42(12):113564. View in: Pubmed

      • Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression. Proc Natl Acad Sci U S A. 2023 Dec 05; 120(49):e2316763120. View in: Pubmed

      • Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer. Mol Cancer Ther. 2023 Nov 01; 22(11):1304-1318. View in: Pubmed

      • HATS off to KAT6A/B inhibitors: A new way to target estrogen-receptor-positive breast cancer. Cell Chem Biol. 2023 10 19; 30(10):1183-1185. View in: Pubmed

      • Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer Cell. 2023 Jul 10; 41(7):1381. View in: Pubmed

      • A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer. Nat Commun. 2023 06 15; 14(1):3561. View in: Pubmed

      • Clinical and translational relevance of intratumor heterogeneity. Trends Cancer. 2023 09; 9(9):726-737. View in: Pubmed

      • Copy Number Variation in Inflammatory Breast Cancer. Cells. 2023 04 04; 12(7). View in: Pubmed

      • Challenges and opportunities for modeling aging and cancer. Cancer Cell. 2023 04 10; 41(4):641-645. View in: Pubmed

      • JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States. Cancer Res. 2023 01 18; 83(2):264-284. View in: Pubmed

      • Breast cancer prevention by short-term inhibition of TGFß signaling. Nat Commun. 2022 12 07; 13(1):7558. View in: Pubmed

      • Molecular classification and biomarkers of clinical outcome in breast ductal carcinoma in situ: Analysis of TBCRC 038 and RAHBT cohorts. Cancer Cell. 2022 12 12; 40(12):1521-1536.e7. View in: Pubmed

      • Untangling the web of intratumour heterogeneity. Nat Cell Biol. 2022 08; 24(8):1192-1201. View in: Pubmed

      • Bacterial Darth Vader: May the force be with you. Cancer Cell. 2022 06 13; 40(6):600-602. View in: Pubmed

      • Report of the First International Symposium on NUT Carcinoma. Clin Cancer Res. 2022 06 13; 28(12):2493-2505. View in: Pubmed

      • Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer. Cancer Immunol Res. 2022 06 03; 10(6):680-697. View in: Pubmed

      • Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress. Proc Natl Acad Sci U S A. 2022 01 18; 119(3). View in: Pubmed

      • A Darwinian perspective on tumor immune evasion. Biochim Biophys Acta Rev Cancer. 2022 01; 1877(1):188671. View in: Pubmed

      • The MCF10 Model of Breast Tumor Progression. Cancer Res. 2021 08 15; 81(16):4183-4185. View in: Pubmed

      • The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2+ breast cancer. JCI Insight. 2021 06 08; 6(11). View in: Pubmed

      • Early-Life Body Adiposity and the Breast Tumor Transcriptome. J Natl Cancer Inst. 2021 06 01; 113(6):778-784. View in: Pubmed

      • Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab. Cancer Discov. 2021 10; 11(10):2474-2487. View in: Pubmed

      • Identifying key questions in the ecology and evolution of cancer. Evol Appl. 2021 Apr; 14(4):877-892. View in: Pubmed

      • Genomic Alterations during the In Situ to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System. Mol Cancer Res. 2021 04; 19(4):623-635. View in: Pubmed

      • Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition. Sci Adv. 2020 06; 6(25):eabb2210. View in: Pubmed

      • Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Mol Cell. 2020 06 18; 78(6):1096-1113.e8. View in: Pubmed

      • Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer. Nat Commun. 2020 05 11; 11(1):2350. View in: Pubmed

      • Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance. Cancer Cell. 2020 04 13; 37(4):471-484. View in: Pubmed

      • Premenopausal Plasma Osteoprotegerin and Breast Cancer Risk: A Case-Control Analysis Nested within the Nurses' Health Study II. Cancer Epidemiol Biomarkers Prev. 2020 06; 29(6):1264-1270. View in: Pubmed

      • Immune Escape during Breast Tumor Progression. Cancer Immunol Res. 2020 04; 8(4):422-427. View in: Pubmed

      • A roadmap for the next decade in cancer research. Nat Cancer. 2020 01; 1(1):12-17. View in: Pubmed

      • Tumor Neoantigens: When Too Much of a Good Thing Is Bad. Cancer Cell. 2019 11 11; 36(5):466-467. View in: Pubmed

      • Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ. Nat Commun. 2019 09 13; 10(1):4182. View in: Pubmed

      • Subclonal cooperation drives metastasis by modulating local and systemic immune microenvironments. Nat Cell Biol. 2019 07; 21(7):879-888. View in: Pubmed

      • EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis. Cancer Res. 2019 08 15; 79(16):4173-4183. View in: Pubmed

      • Metastasis as a systemic disease: molecular insights and clinical implications. Biochim Biophys Acta Rev Cancer. 2019 08; 1872(1):89-102. View in: Pubmed

      • Intratumoral Heterogeneity: More Than Just Mutations. Trends Cell Biol. 2019 07; 29(7):569-579. View in: Pubmed

      • Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment. PLoS Genet. 2019 03; 15(3):e1008002. View in: Pubmed

      • KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance. Cancer Cell. 2019 Feb 11; 35(2):330-332. View in: Pubmed

      • Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment. Cancer Discov. 2019 02; 9(2):176-198. View in: Pubmed

      • Epidemiology, Biology, Treatment, and Prevention of Ductal Carcinoma In Situ (DCIS). JNCI Cancer Spectr. 2018 Nov; 2(4):pky063. View in: Pubmed

      • KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance. Cancer Cell. 2018 12 10; 34(6):939-953.e9. View in: Pubmed

      • TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer. Cell Rep. 2018 10 30; 25(5):1255-1267.e5. View in: Pubmed

      • Intratumor heterogeneity defines treatment-resistant HER2+ breast tumors. Mol Oncol. 2018 11; 12(11):1838-1855. View in: Pubmed

      • Dissecting the mammary gland one cell at a time. Nat Commun. 2018 06 26; 9(1):2473. View in: Pubmed

      • A confetti trail of tumour evolution. Nat Cell Biol. 2018 06; 20(6):639-641. View in: Pubmed

      • Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer. NPJ Breast Cancer. 2018; 4:10. View in: Pubmed

      • Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion. J Pathol. 2017 12; 243(4):496-509. View in: Pubmed

      • Scientific Summary from the Morgan Welch MD Anderson Cancer Center Inflammatory Breast Cancer (IBC) Program 10th Anniversary Conference. J Cancer. 2017; 8(17):3607-3614. View in: Pubmed

      • Classifying the evolutionary and ecological features of neoplasms. Nat Rev Cancer. 2017 10; 17(10):605-619. View in: Pubmed

      • Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition. Cancer Discov. 2017 10; 7(10):1098-1115. View in: Pubmed

      • The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. Nature. 2017 06 15; 546(7658):426-430. View in: Pubmed

      • Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. Cancer Cell. 2017 04 10; 31(4):576-590.e8. View in: Pubmed

      • Precancer Atlas to Drive Precision Prevention Trials. Cancer Res. 2017 04 01; 77(7):1510-1541. View in: Pubmed

      • Mathematical Modeling Links Pregnancy-Associated Changes and Breast Cancer Risk. Cancer Res. 2017 06 01; 77(11):2800-2809. View in: Pubmed

      • G1 cyclins link proliferation, pluripotency and differentiation of embryonic stem cells. Nat Cell Biol. 2017 03; 19(3):177-188. View in: Pubmed

      • BET Bromodomain Proteins as Cancer Therapeutic Targets. Cold Spring Harb Symp Quant Biol. 2016; 81:123-129. View in: Pubmed

      • Expression of estrogen receptor, progesterone receptor, and Ki67 in normal breast tissue in relation to subsequent risk of breast cancer. NPJ Breast Cancer. 2016; 2. View in: Pubmed

      • Spatial Proximity to Fibroblasts Impacts Molecular Features and Therapeutic Sensitivity of Breast Cancer Cells Influencing Clinical Outcomes. Cancer Res. 2016 11 15; 76(22):6495-6506. View in: Pubmed

      • Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer. Cell Rep. 2016 08 16; 16(7):2032-46. View in: Pubmed

      • BRCA1/FANCD2/BRG1-Driven DNA Repair Stabilizes the Differentiation State of Human Mammary Epithelial Cells. Mol Cell. 2016 07 21; 63(2):277-292. View in: Pubmed

      • The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women. Cancer Res. 2016 04 01; 76(7):1926-34. View in: Pubmed

      • Voices of biotech. Nat Biotechnol. 2016 Mar; 34(3):270-5. View in: Pubmed

      • Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature. 2016 Jan 21; 529(7586):413-417. View in: Pubmed

      • Intratumor Heterogeneity in Breast Cancer. Adv Exp Med Biol. 2016; 882:169-89. View in: Pubmed

      • Principles Governing A-to-I RNA Editing in the Breast Cancer Transcriptome. Cell Rep. 2015 Oct 13; 13(2):277-89. View in: Pubmed

      • Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer. Cancer Res. 2015 Oct 15; 75(20):4407-15. View in: Pubmed

      • In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer. Nat Genet. 2015 Oct; 47(10):1212-9. View in: Pubmed

      • Toward understanding and exploiting tumor heterogeneity. Nat Med. 2015 Aug; 21(8):846-53. View in: Pubmed

      • HOXB7 Is an ERa Cofactor in the Activation of HER2 and Multiple ER Target Genes Leading to Endocrine Resistance. Cancer Discov. 2015 Sep; 5(9):944-59. View in: Pubmed

      • Tumorigenesis: it takes a village. Nat Rev Cancer. 2015 Aug; 15(8):473-83. View in: Pubmed

      • Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep. 2015 Jun 16; 11(10):1549-63. View in: Pubmed

      • Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling. BMC Cancer. 2015 Feb 19; 15:70. View in: Pubmed

      • CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer. Cancer Res. 2015 Apr 01; 75(7):1516-26. View in: Pubmed

      • Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells. Stem Cell Reports. 2015 Feb 10; 4(2):297-311. View in: Pubmed

      • Clonal evolution in cancer: a tale of twisted twines. Cell Stem Cell. 2015 Jan 08; 16(1):11-2. View in: Pubmed

      • BRCA1 haploinsufficiency for replication stress suppression in primary cells. Nat Commun. 2014 Nov 17; 5:5496. View in: Pubmed

      • MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 2014 Dec 04; 15(6):762-74. View in: Pubmed

      • Tumor heterogeneity: the Lernaean hydra of oncology? Oncology (Williston Park). 2014 Sep; 28(9):781-2, 784. View in: Pubmed

      • Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature. 2014 Oct 02; 514(7520):54-8. View in: Pubmed

      • JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell. 2014 Jun 16; 25(6):762-77. View in: Pubmed

      • Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. J Biol Chem. 2014 Jun 20; 289(25):17620-33. View in: Pubmed

      • Oncogene-like induction of cellular invasion from centrosome amplification. Nature. 2014 Jun 05; 510(7503):167-71. View in: Pubmed

      • Cancer: Clonal cooperation. Nature. 2014 Apr 03; 508(7494):52-3. View in: Pubmed

      • Tumor heterogeneity confounds and illuminates: a case for Darwinian tumor evolution. Nat Med. 2014 Apr; 20(4):344-6. View in: Pubmed

      • Sorting out the FACS: a devil in the details. Cell Rep. 2014 Mar 13; 6(5):779-81. View in: Pubmed

      • Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep. 2014 Feb 13; 6(3):514-27. View in: Pubmed

      • Genetic and phenotypic diversity in breast tumor metastases. Cancer Res. 2014 Mar 01; 74(5):1338-48. View in: Pubmed

      • Targeting Akt3 signaling in triple-negative breast cancer. Cancer Res. 2014 Feb 01; 74(3):964-73. View in: Pubmed

      • Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell. 2013 Oct 14; 24(4):450-65. View in: Pubmed

      • The RasGAP gene, RASAL2, is a tumor and metastasis suppressor. Cancer Cell. 2013 Sep 09; 24(3):365-78. View in: Pubmed

      • Methylation-specific digital karyotyping of HPV16E6E7-expressing human keratinocytes identifies novel methylation events in cervical carcinogenesis. J Pathol. 2013 Sep; 231(1):53-62. View in: Pubmed

      • Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics. Cell Stem Cell. 2013 Jul 03; 13(1):117-30. View in: Pubmed

      • Tracking tumor resistance using 'liquid biopsies'. Nat Med. 2013 Jun; 19(6):676-7. View in: Pubmed

      • Deconvoluting complex tissues for expression quantitative trait locus-based analyses. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1620):20120363. View in: Pubmed

      • Cancer. Cancer cell phenotypes, in fifty shades of grey. Science. 2013 Feb 01; 339(6119):528-9. View in: Pubmed

      • RNA sequencing of cancer reveals novel splicing alterations. Sci Rep. 2013; 3:1689. View in: Pubmed

      • The expression of Psoriasin (S100A7) and CD24 is linked and related to the differentiation of mammary epithelial cells. PLoS One. 2012; 7(12):e53119. View in: Pubmed

      • A blueprint for an international cancer epigenome consortium. A report from the AACR Cancer Epigenome Task Force. Cancer Res. 2012 Dec 15; 72(24):6319-24. View in: Pubmed

      • Cellular heterogeneity and molecular evolution in cancer. Annu Rev Pathol. 2013 Jan 24; 8:277-302. View in: Pubmed

      • SnapShot: breast cancer. Cancer Cell. 2012 Oct 16; 22(4):562-562.e1. View in: Pubmed

      • The challenges posed by cancer heterogeneity. Nat Biotechnol. 2012 Jul 10; 30(7):604-10. View in: Pubmed

      • On using functional genetics to understand breast cancer biology. Cold Spring Harb Perspect Biol. 2012 Jul 01; 4(7):a013516. View in: Pubmed

      • Sequence analysis of mutations and translocations across breast cancer subtypes. Nature. 2012 Jun 20; 486(7403):405-9. View in: Pubmed

      • Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer. 2012 Apr 19; 12(5):323-34. View in: Pubmed

      • Evolutionary pathways in BRCA1-associated breast tumors. Cancer Discov. 2012 Jun; 2(6):503-11. View in: Pubmed

      • On chromatin remodeling in mammary gland differentiation and breast tumorigenesis. Cold Spring Harb Perspect Biol. 2012 Mar 01; 4(3). View in: Pubmed

      • Progress in breast cancer research. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2715-7. View in: Pubmed

      • Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers. Genes Chromosomes Cancer. 2012 May; 51(5):480-9. View in: Pubmed

      • The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc Natl Acad Sci U S A. 2012 Jan 03; 109(1):221-6. View in: Pubmed

      • PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling. Oncogene. 2012 Jul 19; 31(29):3397-408. View in: Pubmed

      • The microenvironment in breast cancer progression: biology and implications for treatment. Breast Cancer Res. 2011; 13(6):227. View in: Pubmed

      • Heterogeneity in breast cancer. J Clin Invest. 2011 Oct; 121(10):3786-8. View in: Pubmed

      • Unraveling the complexity of basal-like breast cancer. Oncotarget. 2011 Aug; 2(8):588-9. View in: Pubmed

      • The JAK2/STAT3 signaling pathway is required for growth of CD44?CD24? stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011 Jul; 121(7):2723-35. View in: Pubmed

      • Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium. PLoS Genet. 2011 Apr; 7(4):e1001369. View in: Pubmed

      • Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci U S A. 2011 May 10; 108(19):7950-5. View in: Pubmed

      • Functional synergies yet distinct modulators affected by genetic alterations in common human cancers. Cancer Res. 2011 May 15; 71(10):3471-81. View in: Pubmed

      • Targeting the missing links for cancer therapy. Nat Med. 2011 Mar; 17(3):283-4. View in: Pubmed

      • Altered antisense-to-sense transcript ratios in breast cancer. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2820-4. View in: Pubmed

      • Gene expression profiling of human breast tissue samples using SAGE-Seq. Genome Res. 2010 Dec; 20(12):1730-9. View in: Pubmed

      • The origins and implications of intratumor heterogeneity. Cancer Prev Res (Phila). 2010 Nov; 3(11):1361-4. View in: Pubmed

      • Going small is the new big. Nat Methods. 2010 Aug; 7(8):597, 599-600. View in: Pubmed

      • PTK6 regulates IGF-1-induced anchorage-independent survival. PLoS One. 2010 Jul 23; 5(7):e11729. View in: Pubmed

      • The role of the microenvironment in mammary gland development and cancer. Cold Spring Harb Perspect Biol. 2010 Nov; 2(11):a003244. View in: Pubmed

      • PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res. 2010 Jul 15; 70(14):5674-8. View in: Pubmed

      • Stem cells in the human breast. Cold Spring Harb Perspect Biol. 2010 May; 2(5):a003160. View in: Pubmed

      • Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 2010 Feb 01; 16(3):876-87. View in: Pubmed

      • Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations. Oncogene. 2010 Apr 22; 29(16):2337-45. View in: Pubmed

      • Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest. 2010 Feb; 120(2):636-44. View in: Pubmed

      • Molecular markers for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr. 2010; 2010(41):210-3. View in: Pubmed

      • Profiling critical cancer gene mutations in clinical tumor samples. PLoS One. 2009 Nov 18; 4(11):e7887. View in: Pubmed

      • Tumor heterogeneity: causes and consequences. Biochim Biophys Acta. 2010 Jan; 1805(1):105-17. View in: Pubmed

      • Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell. 2009 Nov 06; 16(5):413-24. View in: Pubmed

      • Clonal mutations in the cancer-associated fibroblasts: the case against genetic coevolution. Cancer Res. 2009 Sep 01; 69(17):6765-8; discussion 6769. View in: Pubmed

      • Identification of CD44v6(+)/CD24- breast carcinoma cells in primary human tumors by quantum dot-conjugated antibodies. Lab Invest. 2009 Aug; 89(8):857-66. View in: Pubmed

      • Epigenetic patterns of embryonic and adult stem cells. Cell Cycle. 2009 Mar 15; 8(6):809-17. View in: Pubmed

      • Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009 Apr; 9(4):265-73. View in: Pubmed

      • Origin of carcinoma associated fibroblasts. Cell Cycle. 2009 Feb 15; 8(4):589-95. View in: Pubmed

      • Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A. 2009 Mar 03; 106(9):3372-7. View in: Pubmed

      • Cancer stem cells: a model in the making. Curr Opin Genet Dev. 2009 Feb; 19(1):44-50. View in: Pubmed

      • An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ. Breast Cancer Res. 2009; 11(5):R66. View in: Pubmed

      • Co-evolution of tumor cells and their microenvironment. Trends Genet. 2009 Jan; 25(1):30-8. View in: Pubmed

      • Molecular characterisation of the tumour microenvironment in breast cancer. Eur J Cancer. 2008 Dec; 44(18):2760-5. View in: Pubmed

      • Genome-wide functional synergy between amplified and mutated genes in human breast cancer. Cancer Res. 2008 Nov 15; 68(22):9532-40. View in: Pubmed

      • Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. Breast Cancer Res. 2008; 10(5):R91. View in: Pubmed

      • Detection of psoriasin/S100A7 in the sera of patients with psoriasis. Br J Dermatol. 2009 Feb; 160(2):325-32. View in: Pubmed

      • Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A. 2008 Sep 16; 105(37):14076-81. View in: Pubmed

      • Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression. Clin Cancer Res. 2008 Sep 01; 14(17):5357-67. View in: Pubmed

      • The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008 May 16; 133(4):704-15. View in: Pubmed

      • Regulation of in situ to invasive breast carcinoma transition. Cancer Cell. 2008 May; 13(5):394-406. View in: Pubmed

      • No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas. Nat Genet. 2008 May; 40(5):650-5. View in: Pubmed

      • Breast-cancer stromal cells with TP53 mutations. N Engl J Med. 2008 Apr 10; 358(15):1634-5; author reply 1636. View in: Pubmed

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