Photo of Ian E. Krop,  MD, PhD

Ian E. Krop, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-5958
Fax: (617) 632-4005


ikrop@partners.org

Ian E. Krop, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Instructor in Medicine, Adult Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Chair, Breast Cancer Program, Clinical Research Committee

Research Abstract

My research goal is to identify novel predictive markers and therapeutic targets in breast cancer and translate these discoveries into clinically useful reagents. To accomplish this goal, I have established an ongoing collaboration with Dr Kornelia Polyak to use SAGE (Serial Analysis of Gene Expression) to identify genes important in the interaction between cancerous breast epithelial cells and tumor associated stromal cells. This technology has yielded a number of potential therapeutic targets including two chemokine receptor/ chemokine ligand pairs as well as several cathepsin family members, the expression of which is markedly dysregulated in either tumor epithelial cells and/or tumor associated stromal cells. We are currently validating these proteins as potential targets through the use of small molecule inhibitors in in vitro and in vivo models of tumor-stromal interaction. In addition to this ongoing project, I am directing or co-directing several clinical trials with the aim of identifying novel molecular predictors of response to conventional chemotherapeutic and molecularly targeted therapies.

Publications

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  • Lin NU, Guo H, Yap JT, Mayer IA, Falkson CI, Hobday TJ, Dees EC, Richardson AL, Nanda R, Rimawi MF, Ryabin N, Najita JS, Barry WT, Arteaga CL, Wolff AC, Krop IE, Winer EP, Van den Abbeele AD. Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography I J Clin Oncol 2015. PubMed
  • Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Invest New Drugs 2015. PubMed
  • Ruddy KJ, Guo H, Barry W, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Hudis C, Krop IE, Burstein HJ, Winer EP, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial). Breast Cancer Res Treat 2015; 151:589-96. PubMed
  • Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L. Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer. J Clin Oncol 2015; 33:1136-42. PubMed
  • Goel S, Krop IE. Deciphering the Role of Phosphatidylinositol 3-Kinase Mutations in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. J Clin Oncol 2015. PubMed
  • Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015; 372:134-41. PubMed
  • Toi M, Winer EP, Benson JR, Inamoto T, Forbes JF, von Minckwitz G, Robertson JF, Grobmyer SR, Jatoi I, Sasano H, Kunkler I, Ho AY, Yamauchi C, Chow LW, Huang CS, Han W, Noguchi S, Pegram MD, Yamauchi H, Lee ES, Larionov AA, Bevilacqua JL, Yoshimura M, Sugie T, Yamauchi A, Krop IE, Noh DY, Klimberg VS, . Personalization of loco-regional care for primary breast cancer patients (part 1). Future Oncol 2015; 11:1297-300. PubMed
  • Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Res Treat 2015; 149:151-61. PubMed
  • Toi M, Winer EP, Benson JR, Inamoto T, Forbes JF, von Minckwitz G, Robertson JF, Grobmyer SR, Jatoi I, Sasano H, Kunkler I, Ho AY, Yamauchi C, Chow LW, Huang CS, Han W, Noguchi S, Pegram MD, Yamauchi H, Lee ES, Larionov AA, Bevilacqua JL, Yoshimura M, Sugie T, Yamauchi A, Krop IE, Noh DY, Klimberg VS, . Personalization of loco-regional care for primary breast cancer patients (part 2). Future Oncol 2015; 11:1301-5. PubMed
  • Diéras V, Harbeck N, Budd GT, Greenson JK, Guardino AE, Samant M, Chernyukhin N, Smitt MC, Krop IE. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: an integrated safety analysis. J Clin Oncol 2014; 32:2750-7. PubMed
  • Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, Lim E, Liu W, Bronson RT, Bowden M, Brock J, Krop IE, Dillon DA, Gygi SP, Mills GB, Richardson AL, Signoretti S, Yaffe MB, Kaelin WG. Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell 2014; 26:222-34. PubMed
  • Duda DG, Ancukiewicz M, Isakoff SJ, Krop IE, Jain RK. Seeds and soil: unraveling the role of local tumor stroma in distant metastasis. Journal of the National Cancer Institute 2014. PubMed
  • Krop IE, Kim SB, González-Martín A, LoRusso PM, Ferrero JM, Smitt M, Yu R, Leung AC, Wildiers H, . Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:689-99. PubMed
  • Tolaney SM, Jeong J, Guo H, Brock J, Morganstern D, Come SE, Golshan M, Bellon J, Winer EP, Krop IE. A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer. Cancer Med 2014; 3:293-9. PubMed
  • Krop IE. New Research on the Treatment of Small HER2-Positive Breast Cancers. Clin Adv Hematol Oncol 2014; 12:124-7. PubMed
  • Krop I, Winer EP. Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer. Clin Cancer Res 2014; 20:15-20. PubMed
  • Krop IE, Burstein HJ. Trastuzumab: qui bono? Journal of the National Cancer Institute 2013; 105:1772-5. PubMed
  • Vaz-Luis I, Zeghibe CA, Frank ES, Sohl J, Washington KE, Silverman SG, Fonte JM, Mayer EL, Overmoyer BA, Richardson AL, Krop IE, Winer EP, Lin NU. Prospective clinical experience with research biopsies in breast cancer patients. Breast Cancer Res Treat 2013; 142:203-9. PubMed
  • Metzger-Filho O, Winer EP, Krop I. Pertuzumab: optimizing HER2 blockade. Clin Cancer Res 2013; 19:5552-6. PubMed
  • Kansal KJ, Dominici LS, Tolaney SM, Isakoff SJ, Smith BL, Jiang W, Brock JE, Winer EP, Krop IE, Golshan M. Neoadjuvant bevacizumab: surgical complications of mastectomy with and without reconstruction. Breast Cancer Res Treat 2013; 141:255-9. PubMed
  • Vaz-Luis I, Seah D, Olson EM, Wagle N, Metzger-Filho O, Sohl J, Litsas G, Burstein HJ, Krop IE, Winer EP, Lin NU. Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: a retrospective cohort study. Clin Breast Cancer 2013; 13:254-63. PubMed
  • Rath MG, Masciari S, Gelman R, Miron A, Miron P, Foley K, Richardson AL, Krop IE, Verselis SJ, Dillon DA, Garber JE. Prevalence of germline TP53 mutations in HER2+ breast cancer patients. Breast Cancer Res Treat 2013. PubMed
  • Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, Dorfman D, Pinkus G, Weigert O, Hornick JL, Chirieac LR, Hirsch M, Oh DJ, South AP, Leigh IM, Pourreyron C, Cassidy AJ, Deangelo DJ, Weinstock DM, Krop IE, Dillon D, Brock JE, Lazar AJ, Peto M, Cho RJ, Stoeck A, Haines BB, Sathayanrayanan S, Rodig S, Aster JC. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry. PLoS ONE 2013; 8:e67306. PubMed
  • Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, . Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367:1783-91. PubMed
  • Bender BC, Schaedeli-Stark F, Koch R, Joshi A, Chu YW, Rugo H, Krop IE, Girish S, Friberg LE, Gupta M. A population pharmacokinetic/pharmacodynamic model of thrombocytopenia characterizing the effect of trastuzumab emtansine (T-DM1) on platelet counts in patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol 2012; 70:591-601. PubMed
  • Pettersson F, Yau C, Dobocan MC, Culjkovic-Kraljacic B, Retrouvay H, Puckett R, Flores LM, Krop IE, Rousseau C, Cocolakis E, Borden KL, Benz CC, Miller WH. Ribavirin treatment effects on breast cancers overexpressing eIF4E, a biomarker with prognostic specificity for luminal B-type breast cancer. Clin Cancer Res 2011. PubMed
  • Burris HA, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O'Shaughnessy JA. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 2011; 29:398-405. PubMed
  • Mayer EL, Krop IE. Advances in targeting SRC in the treatment of breast cancer and other solid malignancies. Clin Cancer Res 2010; 16:3526-32. PubMed
  • Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi JH, Sliwkowski MX, Jacobson F, Lutzker SG, Burris HA. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol 2010; 28:2698-704. PubMed
  • Peppercorn J, Shapira I, Collyar D, Deshields T, Lin N, Krop I, Grunwald H, Friedman P, Partridge AH, Schilsky RL, Bertagnolli MM. Ethics of mandatory research biopsy for correlative end points within clinical trials in oncology. J Clin Oncol 2010; 28:2635-40. PubMed
  • Flores LM, Kindelberger DW, Ligon AH, Capelletti M, Fiorentino M, Loda M, Cibas ES, Jänne PA, Krop IE. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer 2010; 102:1495-502. PubMed
  • Yang XH, Flores LM, Li Q, Zhou P, Xu F, Krop IE, Hemler ME. Disruption of Laminin-Integrin-CD151-Focal Adhesion Kinase Axis Sensitizes Breast Cancer Cells to ErbB2 Antagonists. Cancer Res 2010; 70:2256-63. PubMed
  • Tolaney SM,Krop IE. Mechanisms of trastuzumab resistance in breast cancer. Anticancer Agents Med Chem 2009; 9:348-55. PubMed
  • Krop IE, Winer EP. Ten years of HER2-directed therapy: still questions after all these years. Breast Cancer Res Treat 2009; 113:207-9. 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
  • Guix M, Granja Nde M, Meszoely I, Adkins TB, Wieman BM, Frierson KE, Sanchez V, Sanders ME, Grau AM, Mayer IA, Pestano G, Shyr Y, Muthuswamy S, Calvo B, Krontiras H, Krop IE, Kelley MC, Arteaga CL. Short preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers. J Clin Oncol 2008; 26:897-906. PubMed
  • Segara D, Krop IE, Garber JE, Winer E, Harris L, Bellon JR, Birdwell R, Lester S, Lipsitz S, Iglehart JD, Golshan M. Does MRI predict pathologic tumor response in women with breast cancer undergoing preoperative chemotherapy? J Surg Oncol 2007; 96:474-80. PubMed
  • Krop IE. Chemokine signaling in gliomas: prognostic factor, therapeutic target or both? Cancer Biol Ther 2006; 5:1039-41. PubMed
  • Krop I, M. A putative role for psoriasin in breast tumor progression. Cancer Res 2005; 65:11326-34. 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
  • Krop I, Maguire P, Lahti-Domenici J, Lodeiro G, Richardson A, Johannsdottir HK, Nevanlinna H, Borg A, Gelman R, Barkardottir RB, Lindblom A, Polyak K. Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors. Cancer Res 2003; 63:2024-7. PubMed
  • Seth P, Krop I, Porter D, Polyak K. Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression). Oncogene 2002; 21:836-43. PubMed
  • 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
  • Krop IE, Wieczorek TJ, Mayer RJ. Diagnostic dilemmas in oncology. Case 3. Metastatic ovarian cancer simulating colon cancer. J Clin Oncol 2000; 18:3189-92. PubMed
  • Krop I, Shaffer AL, Fearon DT, Schlissel MS. The signaling activity of murine CD19 is regulated during cell development. J Immunol 1996; 157:48-56. PubMed
  • Rolink A, ten Boekel E, Melchers F, Fearon DT, Krop I, Andersson J. A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors. J Exp Med 1996; 183:187-94. PubMed
  • Krop I, de Fougerolles AR, Hardy RR, Allison M, Schlissel MS, Fearon DT. Self-renewal of B-1 lymphocytes is dependent on CD19. Eur J Immunol 1996; 26:238-42. PubMed
  • Bain G, Maandag EC, Izon DJ, Amsen D, Kruisbeek AM, Weintraub BC, Krop I, Schlissel MS, Feeney AJ, van Roon M. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 1994; 79:885-92. PubMed
  • Mehta J, Mehta P, Krop I, Lawson D. The primary wave of epinephrine-induced platelet aggregation represents alpha 2-adrenoceptor status. Thromb Res Suppl 1988; 49:531-7. PubMed
  • Mehta P, Mehta J, Lawson D, Krop I, Letts LG. Leukotrienes potentiate the effects of epinephrine and thrombin on human platelet aggregation. Thromb Res Suppl 1986; 41:731-8. PubMed
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