Photo of Kornelia Polyak,  MD, PhD

Kornelia Polyak, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2106
Fax: (617) 582-8490


Kornelia_Polyak@dfci.harvard.edu

Kornelia Polyak, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Professor of Medicine, Medical Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

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 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 intratumor diversity 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.

We have developed a model of intratumor clonal 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 preliminary 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.

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 being developing breast cancer. This will allow us to identify who needs the 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 must in the breast need to be eliminated to reduce risk? A number of studies have shown that breast epithelial progenitor cells are the 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 we 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.

 

Publications

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  • Jin K, Park S, Teo WW, Korangath P, Cho SS, Yoshida T, Gyorffy B, Goswami CP, Nakshatri H, Cruz LA, Zhou W, Ji H, Su Y, Ekram M, Wu Z, Zhu T, Polyak K, Sukumar S. HOXB7 is an ER留 cofactor in the activation of HER2 and multiple ER target genes leading to endocrine resistance. 2015. PubMed
  • Tabassum DP, Polyak K. Tumorigenesis: it takes a village. Nat Rev Cancer 2015. PubMed
  • Su Y, Subedee A, Bloushtain-Qimron N, Savova V, Krzystanek M, Li L, Marusyk A, Tabassum DP, Zak A, Flacker MJ, Li M, Lin JJ, Sukumar S, Suzuki H, Long H, Szallasi Z, Gimelbrant A, Maruyama R, Polyak K. Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer. Cell Rep 2015; 11:1549-63. PubMed
  • Yoshida T, Kim JH, Carver K, Su Y, Weremowicz S, Mulvey L, Yamamoto S, Brennan C, Mei S, Long H, Yao J, Polyak K. CLK2 Is an Oncogenic Kinase and Splicing Regulator in Breast Cancer. Cancer Res 2015; 75:1516-26. PubMed
  • Huh SJ, Clement K, Jee D, Merlini A, Choudhury S, Maruyama R, Yoo R, Chytil A, Boyle P, Ran FA, Moses HL, Barcellos-Hoff MH, Jackson-Grusby L, Meissner A, Polyak K. Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells. Stem Cell Reports 2015; 4:297-311. PubMed
  • Janiszewska M, Polyak K. Clonal evolution in cancer: a tale of twisted twines. Cell Stem Cell 2015; 16:11-2. PubMed
  • Bancovik J, Moreira DF, Carrasco D, Yao J, Porter D, Moura R, Camargo A, Fontes-Oliveira CC, Malpartida MG, Carambula S, Vannier E, Strauss BE, Wakamatsu A, Alves VA, Logullo AF, Soares FA, Polyak K, Belizário JE. Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling. BMC Cancer 2015; 15:70. PubMed
  • Cuiffo BG, Campagne A, Bell GW, Lembo A, Orso F, Lien EC, Bhasin MK, Raimo M, Hanson SE, Marusyk A, El-Ashry D, Hematti P, Polyak K, Mechta-Grigoriou F, Mariani O, Volinia S, Vincent-Salomon A, Taverna D, Karnoub AE. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell 2014; 15:762-74. PubMed
  • Janiszewska M, Beca F, Polyak K. Tumor heterogeneity: the lernaean hydra of oncology? Oncology (Huntingt) 2014. PubMed
  • Marusyk A, Tabassum DP, Altrock PM, Almendro V, Michor F, Polyak K. Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity. Nature 2014. PubMed
  • Yamamoto S, Wu Z, Russnes HG, Takagi S, Peluffo G, Vaske C, Zhao X, Moen Vollan HK, Maruyama R, Ekram MB, Sun H, Kim JH, Carver K, Zucca M, Feng J, Almendro V, Bessarabova M, Rueda OM, Nikolsky Y, Caldas C, Liu XS, Polyak K. JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer Cell 2014; 25:762-77. PubMed
  • Godinho SA, Picone R, Burute M, Dagher R, Su Y, Leung CT, Polyak K, Brugge JS, Théry M, Pellman D. Oncogene-like induction of cellular invasion from centrosome amplification. Nature 2014. PubMed
  • Zou MR, Cao J, Liu Z, Huh SJ, Polyak K, Yan Q. 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. PubMed
  • Polyak K. Tumor Heterogeneity Confounds and Illuminates: A case for Darwinian tumor evolution. Nat Med 2014; 20:344-6. PubMed
  • Polyak K, Marusyk A. Cancer: Clonal cooperation. Nature 2014; 508:52-3. PubMed
  • Hines WC, Su Y, Kuhn I, Polyak K, Bissell MJ. Sorting out the FACS: a devil in the details. Cell Rep 2014; 6:779-81. PubMed
  • Almendro V, Kim HJ, Cheng YK, Gönen M, Itzkovitz S, Argani P, van Oudenaarden A, Sukumar S, Michor F, Polyak K. Genetic and phenotypic diversity in breast tumor metastases. Cancer Res 2014; 74:1338-48. PubMed
  • Almendro V, Cheng YK, Randles A, Itzkovitz S, Marusyk A, Ametller E, Gonzalez-Farre X, Muñoz M, Russnes HG, Helland A, Rye IH, Borresen-Dale AL, Maruyama R, van Oudenaarden A, Dowsett M, Jones RL, Reis-Filho J, Gascon P, Gönen M, Michor F, Polyak K. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep 2014; 6:514-27. PubMed
  • Chin YR, Yoshida T, Marusyk A, Beck AH, Polyak K, Toker A. Targeting Akt3 signaling in triple-negative breast cancer. Cancer Res 2014; 74:964-73. PubMed
  • Pathania S, Bade S, Le Guillou M, Burke K, Reed R, Bowman-Colin C, Su Y, Ting DT, Polyak K, Richardson AL, Feunteun J, Garber JE, Livingston DM. BRCA1 haploinsufficiency for replication stress suppression in primary cells. Nat Commun 2014; 5:5496. PubMed
  • Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M, Daemen A, Hu M, Chan DA, Ethier SP, van 't Veer LJ, Polyak K, McCormick F, Gray JW. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell 2013; 24:450-65. PubMed
  • McLaughlin SK, Olsen SN, Dake B, De Raedt T, Lim E, Bronson RT, Beroukhim R, Polyak K, Brown M, Kuperwasser C, Cichowski K. The RasGAP gene, RASAL2, is a tumor and metastasis suppressor. Cancer Cell 2013; 24:365-78. PubMed
  • Steenbergen RD, Ongenaert M, Snellenberg S, Trooskens G, van der Meide WF, Pandey D, Bloushtain-Qimron N, Polyak K, Meijer CJ, Snijders PJ, Van Criekinge W. Methylation-specific digital karyotyping of HPV16E6E7-expressing human keratinocytes identifies novel methylation events in cervical carcinogenesis. J Pathol 2013; 231:53-62. PubMed
  • Choudhury S, Almendro V, Merino VF, Wu Z, Maruyama R, Su Y, Martins FC, Fackler MJ, Bessarabova M, Kowalczyk A, Conway T, Beresford-Smith B, Macintyre G, Cheng YK, Lopez-Bujanda Z, Kaspi A, Hu R, Robens J, Nikolskaya T, Haakensen VD, Schnitt SJ, Argani P, Ethington G, Panos L, Grant M, Clark J, Herlihy W, Lin SJ, Chew G, Thompson EW, Greene-Colozzi A, Richardson AL, Rosson GD, Pike M, Garber JE, Nikolsky Y, Blum JL, Au A, Hwang ES, Tamimi RM, Michor F, Haviv I, Liu XS, Sukumar S, Polyak K. Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics. Cell Stem Cell 2013; 13:117-30. PubMed
  • Pantel K, Diaz LA, Polyak K. Tracking tumor resistance using 'liquid biopsies'. Nat Med 2013; 19:676-7. PubMed
  • Seo JH, Li Q, Fatima A, Eklund A, Szallasi Z, Polyak K, Richardson AL, Freedman ML. Deconvoluting complex tissues for expression quantitative trait locus-based analyses. Philos Trans R Soc Lond B Biol Sci 2013; 368:20120363. PubMed
  • Almendro V, Marusyk A, Polyak K. Cellular Heterogeneity and Molecular Evolution in Cancer. Annu Rev Pathol 2012. PubMed
  • Polyak K, Metzger Filho O. SnapShot: Breast Cancer. Cancer Cell 2012; 22:562-562.e1. PubMed
  • Bhatia S, Frangioni JV, Hoffman RM, Iafrate AJ, Polyak K. The challenges posed by cancer heterogeneity. Nat Biotechnol 2012; 30:604-10. PubMed
  • Polyak K. On using functional genetics to understand breast cancer biology. Cold Spring Harb Perspect Biol 2012; 4:a013516. PubMed
  • Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, Frederick AM, Lawrence MS, Sivachenko AY, Sougnez C, Zou L, Cortes ML, Fernandez-Lopez JC, Peng S, Ardlie KG, Auclair D, Bautista-Piña V, Duke F, Francis J, Jung J, Maffuz-Aziz A, Onofrio RC, Parkin M, Pho NH, Quintanar-Jurado V, Ramos AH, Rebollar-Vega R, Rodriguez-Cuevas S, Romero-Cordoba SL, Schumacher SE, Stransky N, Thompson KM, Uribe-Figueroa L, Baselga J, Beroukhim R, Polyak K, Sgroi DC, Richardson AL, Jimenez-Sanchez G, Lander ES, Gabriel SB, Garraway LA, Golub TR, Melendez-Zajgla J, Toker A, Getz G, Hidalgo-Miranda A, Meyerson M. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012; 486:405-9. PubMed
  • Martins FC, De S, Almendro V, Gönen M, Park SY, Blum JL, Herlihy W, Ethington G, Schnitt SJ, Tung N, Garber JE, Fetten K, Michor F, Polyak K. Evolutionary pathways in BRCA1-associated breast tumors. 2012; 2:503-11. PubMed
  • Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer 2012; 12:323-34. PubMed
  • Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, Wu Z, Gönen M, Mulvey LA, Bessarabova MO, Huh SJ, Silver SJ, Kim SY, Park SY, Lee HE, Anderson KS, Richardson AL, Nikolskaya T, Nikolsky Y, Liu XS, Root DE, Hahn WC, Frank DA, Polyak K. The JAK2/STAT3 signaling pathway is required for growth of CD44竅コCD24竅サ stem cell-like breast cancer cells in human tumors. J Clin Invest 2011; 121:2723-35. PubMed
  • Maruyama R, Choudhury S, Kowalczyk A, Bessarabova M, Beresford-Smith B, Conway T, Kaspi A, Wu Z, Nikolskaya T, Merino VF, Lo PK, Liu XS, Nikolsky Y, Sukumar S, Haviv I, Polyak K. Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium. PLoS Genet. 2011; 7:e1001369. PubMed
  • Bessarabova M, Pustovalova O, Shi W, Serebriyskaya T, Ishkin A, Polyak K, Velculescu VE, Nikolskaya T, Nikolsky Y. Functional synergies yet distinct modulators affected by genetic alterations in common human cancers. Cancer Res 2011. PubMed
  • Polyak K, Garber J. Targeting the missing links for cancer therapy. Nat Med 2011; 17:283-4. PubMed
  • Wu ZJ, Meyer CA, Choudhury S, Shipitsin M, Maruyama R, Bessarabova M, Nikolskaya T, Sukumar S, Schwartzman A, Liu JS, Polyak K, Liu XS. Gene expression profiling of human breast tissue samples using SAGE-Seq. Genome Res 2010; 20:1730-9. PubMed
  • Maruyama R, Shipitsin M, Choudhury S, Wu Z, Protopopov A, Yao J, Lo PK, Bessarabova M, Ishkin A, Nikolsky Y, Liu XS, Sukumar S, Polyak K. Breast Cancer Special Feature: Altered antisense-to-sense transcript ratios in breast cancer. Proc Natl Acad Sci U S A 2010. PubMed
  • Michor F, Polyak K. The Origins and Implications of Intratumor Heterogeneity. Cancer Prev Res (Phila Pa) 2010; 3:1361-4. PubMed
  • Polyak K, Kalluri R. The Role of the Microenvironment in Mammary Gland Development and Cancer. Cold Spring Harb Perspect Biol 2010; 2:a003244. PubMed
  • Polyak K. Going small is the new big. Nat Methods 2010; 7:597, 599-600. PubMed
  • Miron A, Varadi M, Carrasco D, Li H, Luongo L, Kim HJ, Park SY, Cho EY, Lewis G, Kehoe S, Iglehart JD, Dillon D, Allred DC, Macconaill L, Gelman R, Polyak K. PIK3CA mutations in in situ and invasive breast carcinomas. Cancer Res 2010; 70:5674-8. PubMed
  • Petersen OW, Polyak K. Stem cells in the human breast. Cold Spring Harb Perspect Biol 2010; 2:a003160. PubMed
  • Park SY, Lee HE, Li H, Shipitsin M, Gelman R, Polyak K. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 2010; 16:876-87. PubMed
  • Park SY, Gönen M, Kim HJ, Michor F, Polyak K. Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest 2010; 120:636-44. PubMed
  • Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 2010; 1805:105-17. PubMed
  • Polyak K. Molecular markers for the diagnosis and management of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010; 2010:210-3. PubMed
  • Irie HY, Shrestha Y, Selfors LM, Frye F, Iida N, Wang Z, Zou L, Yao J, Lu Y, Epstein CB, Natesan S, Richardson AL, Polyak K, Mills GB, Hahn WC, Brugge JS. PTK6 regulates IGF-1-induced anchorage-independent survival. PLoS ONE 2010; 5:e11729. PubMed
  • Zhang Q, Gu J, Li L, Liu J, Luo B, Cheung HW, Boehm JS, Ni M, Geisen C, Root DE, Polyak K, Brown M, Richardson AL, Hahn WC, Kaelin WG, Bommi-Reddy A. Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell 2009; 16:413-24. PubMed
  • Campbell I, Polyak K, Haviv I. Clonal mutations in the cancer-associated fibroblasts: the case against genetic coevolution. Cancer Res 2009; 69:6765-8; discussion 6769. PubMed
  • Snyder EL,Bailey D,Shipitsin M,Polyak K,Loda M. Identification of CD44v6(+)/CD24- breast carcinoma cells in primary human tumors by quantum dot-conjugated antibodies. Lab Invest 2009; 89:857-66. PubMed
  • Polyak K,Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 2009; 9:265-73. PubMed
  • Bloushtain-Qimron N,Yao J,Shipitsin M,Maruyama R,Polyak K. Epigenetic patterns of embryonic and adult stem cells. Cell Cycle 2009; 8:809-17. PubMed
  • Hu M,Peluffo G,Chen H,Gelman R,Schnitt S,Polyak K. 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; 106:3372-7. PubMed
  • Haviv I,Polyak K,Qiu W,Hu M,Campbell I. Origin of carcinoma associated fibroblasts. Cell Cycle 2009; 8:589-95. PubMed
  • Marotta LL,Polyak K. Cancer stem cells: a model in the making. Curr Opin Genet Dev 2009; 19:44-50. PubMed
  • MacConaill LE, Campbell CD, Kehoe SM, Bass AJ, Hatton C, Niu L, Davis M, Yao K, Hanna M, Mondal C, Luongo L, Emery CM, Baker AC, Philips J, Goff DJ, Fiorentino M, Rubin MA, Polyak K, Chan J, Wang Y, Fletcher JA, Santagata S, Corso G, Roviello F, Shivdasani R, Kieran MW, Ligon KL, Stiles CD, Hahn WC, Meyerson ML, Garraway LA. Profiling critical cancer gene mutations in clinical tumor samples. PLoS ONE 2009; 4:e7887. PubMed
  • Polyak K,Haviv I,Campbell IG. Co-evolution of tumor cells and their microenvironment. Trends Genet 2008; 25:30-8. PubMed
  • Hu M,Polyak K. Molecular characterisation of the tumour microenvironment in breast cancer. Eur J Cancer 2008; 44:2760-5. PubMed
  • Nikolsky Y,Sviridov E,Yao J,Dosymbekov D,Ustyansky V,Kaznacheev V,Dezso Z,Mulvey L,Macconaill LE,Winckler W,Serebryiskaya T,Nikolskaya T,Polyak K. Genome-wide functional synergy between amplified and mutated genes in human breast cancer. Cancer Res 2008; 68:9532-40. PubMed
  • Bloushtain-Qimron N,Yao J,Snyder EL,Shipitsin M,Campbell LL,Mani SA,Hu M,Chen H,Ustyansky V,Antosiewicz JE,Argani P,Halushka MK,Thomson JA,Pharoah P,Porgador A,Sukumar S,Parsons R,Richardson AL,Stampfer MR,Gelman RS,Nikolskaya T,Nikolsky Y,Polyak K. Cell type-specific DNA methylation patterns in the human breast. Proc Natl Acad Sci U S A 2008; 105:14076-81. PubMed
  • Kleer CG,Bloushtain-Qimron N,Chen YH,Carrasco D,Hu M,Yao J,Kraeft SK,Collins LC,Sabel MS,Argani P,Gelman R,Schnitt SJ,Krop IE,Polyak K. Epithelial and stromal cathepsin K and CXCL14 expression in breast tumor progression. Clin Cancer Res 2008; 14:5357-67. PubMed
  • Mani SA,Guo W,Liao MJ,Eaton EN,Ayyanan A,Zhou AY,Brooks M,Reinhard F,Zhang CC,Shipitsin M,Campbell LL,Polyak K,Brisken C,Yang J,Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133:704-15. PubMed
  • Shipitsin M, Polyak K. The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 2008; 88:459-63. PubMed
  • Qiu W, Hu M, Sridhar A, Opeskin K, Fox S, Shipitsin M, Trivett M, Thompson ER, Ramakrishna M, Gorringe KL, Polyak K, Haviv I, Campbell IG. No evidence of clonal somatic genetic alterations in cancer-associated fibroblasts from human breast and ovarian carcinomas. Nat Genet 2008; 40:650-5. PubMed
  • Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, Richardson A, Violette S, Nikolskaya T, Nikolsky Y, Bauerlein EL, Hahn WC, Gelman RS, Allred C, Bissell MJ, Schnitt S, Polyak K. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell 2008; 13:394-406. PubMed
  • Campbell IG, Qiu W, Polyak K, Haviv I. Breast-cancer stromal cells with TP53 mutations. N Engl J Med 2008; 358:1634-5; author reply 1636. PubMed
  • Hu M, Polyak K. Microenvironmental regulation of cancer development. Curr Opin Genet Dev 2008; 18:27-34. PubMed
  • Zhao X, Goswami M, Pokhriyal N, Ma H, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H, Band V. Cyclooxygenase-2 expression during immortalization and breast cancer progression. Cancer Res 2008; 68:467-75. PubMed
  • Polyak K. Is breast tumor progression really linear? Clin Cancer Res 2008; 14:339-41. PubMed
  • Cao D,Polyak K,Halushka MK,Nassar H,Kouprina N,Iacobuzio-Donahue C,Wu X,Sukumar S,Hicks J,De Marzo A,Argani P. 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:R91. PubMed
  • Paruchuri V, Prasad A, McHugh K, Bhat HK, Polyak K, Ganju RK. S100A7-downregulation inhibits epidermal growth factor-induced signaling in breast cancer cells and blocks osteoclast formation. PLoS ONE 2008; 3:e1741. PubMed
  • Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B. The genomic landscapes of human breast and colorectal cancers. Science 2007; 318:1108-13. PubMed
  • Polyak K. Breast cancer: origins and evolution. J Clin Invest 2007; 117:3155-63. PubMed
  • Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449:557-63. PubMed
  • Blackshaw S, Croix BS, Polyak K, Kim JB, Cai L. Serial analysis of gene expression (SAGE): experimental method and data analysis. Curr Protoc Mol Biol 2008; Chapter 25:Unit 25B.6. PubMed
  • Campbell LL, Polyak K. Breast tumor heterogeneity: cancer stem cells or clonal evolution? Cell Cycle 2007; 6:2332-8. PubMed
  • Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Richardson AL, Greulich H, Stewart CJ, Mulvey LA, Shen RR, Ambrogio L, Hirozane-Kishikawa T, Hill DE, Vidal M, Meyerson M, Grenier JK, Hinkle G, Root DE, Roberts TM, Lander ES, Polyak K, Hahn WC. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 2007; 129:1065-79. PubMed
  • Polyak K. Breast cancer stem cells: a case of mistaken identity? Stem Cell Rev 2007; 3:107-9. PubMed
  • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11:259-73. PubMed
  • Polyak K. The p27Kip1 tumor suppressor gene: Still a suspect or proven guilty? Cancer Cell 2006; 10:352-4. PubMed
  • Yao J, Weremowicz S, Feng B, Gentleman RC, Marks JR, Gelman R, Brennan C, Polyak K. Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression. Cancer Res 2006; 66:4065-78. PubMed
  • Polyak K, Hahn WC. Roots and stems: stem cells in cancer. Nat Med 2006; 12:296-300. PubMed
  • Polyak K. Pregnancy and breast cancer: the other side of the coin. Cancer Cell 2006; 9:151-3. PubMed
  • Porter D, Yao J, Polyak K. SAGE and related approaches for cancer target identification. Drug Discov Today 2006; 11:110-8. PubMed
  • Hu M, Polyak K. Serial analysis of gene expression. Nat Protoc 2007; 1:1743-60. PubMed
  • Hu M, Yao J, Polyak K. Methylation-specific digital karyotyping. Nat Protoc 2007; 1:1406-11. PubMed
  • Krop I, M. A putative role for psoriasin in breast tumor progression. Cancer Res 2005; 65:11326-34. PubMed
  • Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K. HIN-1, an inhibitor of cell growth, invasion, and AKT activation. Cancer Res 2005; 65:9659-69. PubMed
  • Hu M, Yao J, Cai L, Bachman KE, van den Br. Distinct epigenetic changes in the stromal cells of breast cancers. Nat Genet 2005; 37:899-905. PubMed
  • Polyak K, Hu M. Do myoepithelial cells hold the key for breast tumor progression? J Mammary Gland Biol Neoplasia 2006; 10:231-47. PubMed
  • Krop I, Player A, Tablante A, Taylor-Parker M, Lahti-Domenici J, Fukuoka J, Batra SK, Papadopoulos N, Richards WG, Sugarbaker DJ, Wright RL, Shim J, Stamey TA, Sellers WR, Loda M, Meyerson M, Hruban R, Jen J, Polyak K. Frequent HIN-1 Promoter Methylation and Lack of Expression in Multiple Human Tumor Types. Mol Cancer Res 2004; 2:489-94. PubMed
  • Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell 2004; 6:17-32. PubMed
  • Burstein HJ, Polyak K, Wong JS, Lester SC, Kaelin CM. Ductal carcinoma in situ of the breast. N Engl J Med 2004; 350:1430-41. PubMed
  • Porter D, Polyak K. Cancer target discovery using SAGE. Expert Opin Ther Targets 2003; 7:759-69. PubMed
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  • Enerb. Psoriasin expression in mammary epithelial cells in vitro and in vivo. Cancer Res 2002; 62:43-7. PubMed
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  • Krop IE, Sgroi D, Porter DA, Lunetta KL, LeVangie R, Seth P, Kaelin CM, Rhei E, Bosenberg M, Schnitt S, Marks JR, Pagon Z, Belina D, Razumovic J, Polyak K. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proc Natl Acad Sci U S A 2001; 98:9796-801. PubMed
  • Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, Polyak K. A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Res 2001; 61:5697-702. PubMed
  • Polyak K, Riggins GJ. Gene discovery using the serial analysis of gene expression technique: implications for cancer research. J Clin Oncol 2001; 19:2948-58. PubMed
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