Photo of Panagiotis A. Konstantinopoulos,  MD, PhD

Panagiotis A. Konstantinopoulos, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


panagiotisa_konstantinopoulos@dfci.harvard.edu

Panagiotis A. Konstantinopoulos, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Attending Oncologist, Gynecologic Medical Oncology, Dana-Farber Cancer Institute
  • Director Translational Research, Gynecologic Medical Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

During my career as an academic medical oncologist, I have been able to develop a translational research expertise in ovarian cancer and other gynecologic malignancies with an important niche in the areas of DNA Damage and Repair, bioinformatics and biomarker research. My research has focused on unraveling mechanisms of resistance to chemotherapy and targeted agents, developing the rationale and preclinical data for novel drug combinations in ovarian cancer, and on identification of novel diagnostic and predictive biomarkers of therapeutic response in ovarian cancer as well investigating their mechanistic implication in carcinogenesis. This has led to multiple peer-reviewed publications, acquisition of competitive funding as a PI from diverse Harvard-wide, industry and national sources, invitations to present in regional, national and international oncology meetings, and have directly led to development of clinical trials in gynecologic malignancies.

Publications

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  • Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ, Feltmate CM, Nucci MR, Swisher EM, Nguyen H, Yang C, Morizane R, Kochupurakkal BS, Do KT, Konstantinopoulos PA, Liu JF, Bonventre JV, Matulonis UA, Shapiro GI, Berkowitz RS, Crum CP, D'Andrea AD. Prediction of DNA Repair Inhibitor Response in Short Term Patient-Derived Ovarian Cancer Organoids. 2018. PubMed
  • Konstantinopoulos PA, Brady WE, Farley J, Armstrong A, Uyar DS, Gershenson DM. Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001). Gynecol Oncol 2018; 150:9-13. PubMed
  • Gockley AA, Kolin DL, Awtrey CS, Lindeman NI, Matulonis UA, Konstantinopoulos PA. Durable response in a woman with recurrent low-grade endometrioid endometrial cancer and a germline BRCA2 mutation treated with a PARP inhibitor. Gynecol Oncol 2018. PubMed
  • Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: a trailblazing and transformative journey. Clin Cancer Res 2018. PubMed
  • Ditzel HM, Strickland KC, Meserve EE, Stover E, Konstantinopoulos PA, Matulonis UA, Muto MG, Liu JF, Feltmate C, Horowitz N, Berkowitz RS, Gupta M, Hecht JL, Lin DI, Jochumsen KM, Welch WR, Hirsch MS, Quade BJ, Lee KR, Crum CP, Mutter GL, Nucci MR, Howitt BE. Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC). Int J Gynecol Pathol 2018. PubMed
  • Meghani K, Fuchs W, Detappe A, Drané P, Gogola E, Rottenberg S, Jonkers J, Matulonis U, Swisher EM, Konstantinopoulos PA, Chowdhury D. Multifaceted Impact of MicroRNA 493-5p on Genome-Stabilizing Pathways Induces Platinum and PARP Inhibitor Resistance in BRCA2-Mutated Carcinomas. Cell Rep 2018; 23:100-111. PubMed
  • Mouw KW, Konstantinopoulos PA. From checkpoint to checkpoint: DNA damage ATR/Chk1 checkpoint signalling elicits PD-L1 immune checkpoint activation. Br J Cancer 2018; 118:933-935. PubMed
  • Rondinelli B, Gogola E, Yücel H, Duarte AA, van de Ven M, van der Sluijs R, Konstantinopoulos PA, Jonkers J, Ceccaldi R, Rottenberg S, D'Andrea AD. EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat Cell Biol 2017; 19:1371-1378. PubMed
  • Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA Damage and Repair Biomarkers of Immunotherapy Response. 2017; 7:675-693. PubMed
  • Fendler W, Malachowska B, Meghani K, Konstantinopoulos PA, Guha C, Singh VK, Chowdhury D. Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates. Sci Transl Med 2017. PubMed
  • Shukla SA, Howitt BE, Wu CJ, Konstantinopoulos PA. Predicted neoantigen load in non-hypermutated endometrial cancers: Correlation with outcome and tumor-specific genomic alterations. Gynecol Oncol Rep 2017; 19:42-45. PubMed
  • Howitt BE, Strickland KC, Sholl LM, Rodig S, Ritterhouse LL, Chowdhury D, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression. Oncoimmunology 2017; 6:e1277308. PubMed
  • Stover EH, Konstantinopoulos PA, Matulonis UA, Swisher EM. Biomarkers of Response and Resistance to DNA Repair Targeted Therapies. Clin Cancer Res 2016. PubMed
  • Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte AA, Lee JE, Wong N, Lafarga V, Calvo JA, Panzarino NJ, John S, Day A, Crespo AV, Shen B, Starnes LM, de Ruiter JR, Daniel JA, Konstantinopoulos PA, Cortez D, Cantor SB, Fernandez-Capetillo O, Ge K, Jonkers J, Rottenberg S, Sharan SK, Nussenzweig A. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature 2016; 535:382-7. PubMed
  • Poole EM, Konstantinopoulos PA, Terry KL. Prognostic implications of reproductive and lifestyle factors in ovarian cancer. Gynecol Oncol 2016. PubMed
  • Hu H, Luo ML, Desmedt C, Nabavi S, Yadegarynia S, Hong A, Konstantinopoulos PA, Gabrielson E, Hines-Boykin R, Pihan G, Yuan X, Sotirious C, Dittmer DP, Fingeroth JD, Wulf GM. Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation. EBioMedicine 2016. PubMed
  • Ritterhouse LL, Nowak JA, Strickland KC, Garcia EP, Jia Y, Lindeman NI, Macconaill LE, Konstantinopoulos PA, Matulonis UA, Liu J, Berkowitz RS, Nucci MR, Crum CP, Sholl LM, Howitt BE. Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas. Mod Pathol 2016. PubMed
  • Strickland KC, Howitt BE, Shukla SA, Rodig S, Ritterhouse LL, Liu JF, Garber JE, Chowdhury D, Wu CJ, D'Andrea AD, Matulonis UA, Konstantinopoulos PA. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer. 2016. PubMed
  • Choi YE, Meghani K, Brault ME, Leclerc L, He YJ, Day TA, Elias KM, Drapkin R, Weinstock DM, Dao F, Shih KK, Matulonis U, Levine DA, Konstantinopoulos PA, Chowdhury D. Platinum and PARP Inhibitor Resistance Due to Overexpression of MicroRNA-622 in BRCA1-Mutant Ovarian Cancer. Cell Rep 2016; 14:429-39. PubMed
  • Liu J, Konstantinopoulos PA, Matulonis UA. Genomic testing and precision medicine - what does this mean for gynecologic oncology? Gynecol Oncol 2015. PubMed
  • Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, Stover E, Strickland KC, D'Andrea AD, Wu CJ, Matulonis UA, Konstantinopoulos PA. Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1. JAMA Oncol 2015. PubMed
  • Guillemette S, Serra RW, Peng M, Hayes JA, Konstantinopoulos PA, Green MR, Cantor SB. Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4. Genes Dev 2015; 29:489-94. PubMed
  • Ceccaldi R, O'Connor KW, Mouw KW, Li AY, Matulonis UA, D'Andrea AD, Konstantinopoulos PA. A unique subset of epithelial ovarian cancers with platinum sensitivity and PARP inhibitor resistance. Cancer Res 2015; 75:628-34. PubMed
  • Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B, Petalcorin MI, O'Connor KW, Konstantinopoulos PA, Elledge SJ, Boulton SJ, Yusufzai T, D'Andrea AD. Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair. Nature 2015; 518:258-62. PubMed
  • Konstantinopoulos PA, Matulonis UA. POLE mutations as an alternative pathway for microsatellite instability in endometrial cancer: implications for Lynch syndrome testing. Cancer 2015. PubMed
  • Mouw KW, D'Andrea AD, Konstantinopoulos PA. Nucleotide excision repair (NER) alterations as evolving biomarkers and therapeutic targets in epithelial cancers. Oncoscience 2016; 2:942-3. PubMed
  • Viswanathan AN, Lee LJ, Eswara JR, Horowitz NS, Konstantinopoulos PA, Mirabeau-Beale KL, Rose BS, von Keudell AG, Wo JY. Complications of pelvic radiation in patients treated for gynecologic malignancies. Cancer 2014. PubMed
  • Shah MM, Dobbin ZC, Nowsheen S, Wielgos M, Katre AA, Alvarez RD, Konstantinopoulos PA, Yang ES, Landen CN. An ex vivo assay of XRT-induced Rad51 foci formation predicts response to PARP-inhibition in ovarian cancer. Gynecol Oncol 2014. PubMed
  • Konstantinopoulos PA, Wilson AJ, Saskowski J, Wass E, Khabele D. Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer. Gynecol Oncol 2014. PubMed
  • Choi YE, Battelli C, Watson J, Liu J, Curtis J, Morse AN, Matulonis UA, Chowdhury D, Konstantinopoulos PA. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells. 2014; 5:2678-87. PubMed
  • Hecht JL, Konstantinopoulos PA, Awtrey CS, Soslow RA. Immunohistochemical loss of BRCA1 protein in uterine serous carcinoma. Int J Gynecol Pathol 2014; 33:282-7. PubMed
  • Liu JF, Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. Gynecol Oncol 2014; 133:362-9. PubMed
  • Aird KM, Li H, Xin F, Konstantinopoulos PA, Zhang R. Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer. Cell Cycle 2014; 13:199-207. PubMed
  • Naumann RW, Coleman RL, Burger RA, Sausville EA, Kutarska E, Ghamande SA, Gabrail NY, Depasquale SE, Nowara E, Gilbert L, Gersh RH, Teneriello MG, Harb WA, Konstantinopoulos PA, Penson RT, Symanowski JT, Lovejoy CD, Leamon CP, Morgenstern DE, Messmann RA. PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. J Clin Oncol 2013; 31:4400-6. PubMed
  • Pedersen BS, Konstantinopoulos PA, Spillman MA, De S. Copy neutral loss of heterozygosity is more frequent in older ovarian cancer patients. Genes Chromosomes Cancer 2013; 52:794-801. PubMed
  • Battelli C, Campo M, Buss MK, Awtrey CS, Konstantinopoulos PA. Safety and outcome of patients treated with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary peritoneal or fallopian tube cancer. Chemotherapy 2014; 59:251-9. PubMed
  • Konstantinopoulos PA, Matulonis UA. Current status and evolution of preclinical drug development models of epithelial ovarian cancer. 2013; 3:296. PubMed
  • Fountzilas E, Kelly AD, Perez-Atayde AR, Goldsmith J, Konstantinopoulos PA, Francoeur N, Correll M, Rubio R, Hu L, Gebhardt MC, Quackenbush J, Spentzos D. A microRNA activity map of human mesenchymal tumors: connections to oncogenic pathways; an integrative transcriptomic study. BMC Genomics 2012; 13:332. PubMed
  • Konstantinopoulos PA, Spentzos D, Fountzilas E, Francoeur N, Sanisetty S, Grammatikos AP, Hecht JL, Cannistra SA. Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res 2011. PubMed
  • Konstantinopoulos PA, Cannistra SA, Fountzilas H, Culhane A, Pillay K, Rueda B, Cramer D, Seiden M, Birrer M, Coukos G, Zhang L, Quackenbush J, Spentzos D. Integrated analysis of multiple microarray datasets identifies a reproducible survival predictor in ovarian cancer. PLoS ONE 2011; 6:e18202. PubMed
  • Konstantinopoulos PA, Spentzos D, Karlan BY, Taniguchi T, Fountzilas E, Francoeur N, Levine DA, Cannistra SA. Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 2010; 28:3555-61. PubMed
  • Zachos I, Konstantinopoulos PA, Tzortzis V, Gravas S, Karatzas A, Karamouzis MV, Melekos M, Papavassiliou AG. Systemic therapy of metastatic bladder cancer in the molecular era: current status and future promise. Expert Opin Investig Drugs 2010; 19:875-87. PubMed
  • Konstantinopoulos PA, Fountzilas E, Goldsmith JD, Bhasin M, Pillay K, Francoeur N, Libermann TA, Gebhardt MC, Spentzos D. Analysis of multiple sarcoma expression datasets: implications for classification, oncogenic pathway activation and chemotherapy resistance. PLoS ONE 2010; 5:e9747. PubMed
  • Zachos I,Konstantinopoulos PA,Vandoros GP,Karamouzis MV,Papatsoris AG,Podimatas T,Papachristodoulou A,Chrisofos M,Deliveliotis C,Papavassiliou AG. Predictive value of telomerase reverse transcriptase expression in patients with high risk superficial bladder cancer treated with adjuvant BCG immunotherapy. J Cancer Res Clin Oncol 2009; 135:1169-75. PubMed
  • Kassimatis TI, Konstantinopoulos PA. Rosuvastatin in patients undergoing hemodialysis. N Engl J Med 2009; 361:93; author reply 94-5. PubMed
  • Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. Lancet Oncol 2009; 10:709-17. PubMed
  • Burga LN,Tung NM,Troyan SL,Bostina M,Konstantinopoulos PA,Fountzilas H,Spentzos D,Miron A,Yassin YA,Lee BT,Wulf GM. Altered proliferation and differentiation properties of primary mammary epithelial cells from BRCA1 mutation carriers. Cancer Res 2009; 69:1273-8. PubMed
  • Konstantinopoulos PA, Spentzos D, Cannistra SA. Gene-expression profiling in epithelial ovarian cancer. Nat Clin Pract Oncol 2008; 5:577-87. PubMed
  • Konstantinopoulos PA, Goldsztein H, Dezube BJ, Pantanowitz L. Acquired immunodeficiency syndrome related Kaposi's sarcoma eroding the maxillary bone. J Laryngol Otol 2007; 122:993-7. PubMed
  • Konstantinopoulos PA,Fountzilas E,Pillay K,Zerbini LF,Libermann TA,Cannistra SA,Spentzos D. Carboplatin-induced gene expression changes in vitro are prognostic of survival in epithelial ovarian cancer. BMC Med Genomics 2008; 1:59. PubMed
  • Konstantinopoulos PA, Dezube BJ, Pantanowitz L, Horowitz GL, Beckwith BA. Protein electrophoresis and immunoglobulin analysis in HIV-infected patients. Am J Clin Pathol 2007; 128:596-603. PubMed
  • Konstantinopoulos PA, Sullivan RJ, Karamouzis MV, Dezube BJ. Investigational agents for treatment of AIDS-related Kaposi's sarcoma. Expert Opin Investig Drugs 2007; 16:495-504. PubMed
  • Konstantinopoulos PA, Dezube BJ, March D, Pantanowitz L. HIV-associated intramammary lymphadenopathy. Breast J 2007; 13:192-5. PubMed
  • Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, Di Trolio R, De Placido S, Dezube BJ. Management of AIDS-related Kaposi's sarcoma. Lancet Oncol 2007; 8:167-76. PubMed
  • Rosenblatt J, Wu Z, Vasir B, Zarwan C, Stone R, Mills H, Friedman T, Konstantinopoulos PA, Spentzos D, Ghebremichael M, Stevenson K, Neuberg D, Levine JD, Joyce R, Tzachanis D, Boussiotis V, Kufe D, Avigan D. Generation of Tumor-specific T Lymphocytes Using Dendritic Cell/Tumor Fusions and Anti-CD3/CD28. J Immunother 2010; 33:155-66. PubMed
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