Gynecologic Cancers Program

The DF/HCC Gynecologic Cancers Program seeks to improve methods of prevention, early detection, biological and genetic understanding, diagnosis, and treatment of ovarian cancer. Ovarian cancer is the fifth-leading cause of cancer death in U.S. women and presents at an advanced stage in the majority of affected women. The Program’s ambitious research agenda focuses on a spectrum of scientific issues extending from basic investigations of ovarian cancer biology, through an analysis of genomic, biological, immunotherapeutic, and DNA repair abnormality approach directly from clinical specimens, to efforts aimed at testing novel clinical therapeutics. The program addresses the different histologic subtypes of ovarian cancer as well as this cancer’s molecular pathways, the importance of DNA repair to underlying biology, immunology and the tumor microenvironment, early detection and diagnostics, and clinical trials.

The Gynecologic Cancers Program is multi-disciplinary, multi-institutional, and includes clinical, translational and laboratory-based research efforts. The Program includes basic scientists, medical oncologists, gynecologic oncology surgeons, radiation oncologists, immunologists, pathologists, epidemiologists and biostatisticians, and geneticists. We currently have 65 members in the Gynecologic Cancers program.

Recent Publications

  • Arend RC, Monk BJ, Shapira-Frommer R, Haggerty AF, Alvarez EA, Amit A, Alvarez Secord A, Muller C, Casado Herraez A, Herzog TJ, Tewari KS, Cohen JG, Huang M, Yachnin A, Holeman LL, Ledermann JA, Rachmilewitz Minei T, Buyse M, Fain Shmueli S, Lavi M, Harats D, Penson RT, . Ofranergene Obadenovec (Ofra-Vec, VB-111) With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer: Randomized Controlled Phase III Trial (OVAL Study/GOG 3018). J Clin Oncol 2023. PubMed
  • Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol 2023. PubMed
  • Konstantinopoulos PA, Lee EK, Xiong N, Krasner C, Campos S, Kolin DL, Liu JF, Horowitz N, Wright AA, Bouberhan S, Penson RT, Yeku O, Bowes B, Needham H, Hayes M, Sawyer H, Polak M, Shea M, Cheng SC, Castro C, Matulonis UA. A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer. J Clin Oncol 2022. PubMed
  • Konstantinopoulos PA, Gockley AA, Xiong N, Krasner C, Horowitz N, Campos S, Wright AA, Liu JF, Shea M, Yeku O, Castro C, Polak M, Lee EK, Sawyer H, Bowes B, Moroney J, Cheng SC, Tayob N, Bouberhan S, Spriggs D, Penson RT, Fleming GF, Nucci MR, Matulonis UA. Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer. JAMA Oncol 2022. PubMed
  • Huang C, Lv X, Chen P, Liu J, He C, Chen L, Wang H, Moness ML, Dong J, Rueda BR, Davis JS, Wang C. Human papillomavirus targets the YAP1-LATS2 feedback loop to drive cervical cancer development. Oncogene 2022. PubMed
  • Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol 2022. PubMed
  • Konstantinopoulos PA, da Costa AABA, Gulhan D, Lee EK, Cheng SC, Hendrickson AEW, Kochupurakkal B, Kolin DL, Kohn EC, Liu JF, Stover EH, Curtis J, Tayob N, Polak M, Chowdhury D, Matulonis UA, Färkkilä A, D'Andrea AD, Shapiro GI. A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer. Nat Commun 2021; 12:5574. PubMed
  • Zhou J, Gelot C, Pantelidou C, Li A, Yücel H, Davis RE, Farkkila A, Kochupurakkal B, Syed A, Shapiro GI, Tainer JA, Blagg BSJ, Ceccaldi R, D'Andrea AD. A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors. 2021; 2:598-610. PubMed
  • Stasenko M, Smith E, Yeku O, Park KJ, Laster I, Lee K, Walderich S, Spriggs E, Rueda B, Weigelt B, Zamarin D, Rao TD, Spriggs DR. Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies. Sci Rep 2021; 11:3718. PubMed
  • Iyer S, Zhang S, Yucel S, Horn H, Smith SG, Reinhardt F, Hoefsmit E, Assatova B, Casado J, Meinsohn MC, Barrasa MI, Bell GW, Pérez-Villatoro F, Huhtinen K, Hynninen J, Oikkonen J, Galhenage PM, Pathania S, Hammond PT, Neel BG, Farkkila A, Pépin D, Weinberg RA. Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy. 2021; 11:384-407. PubMed
  • Konstantinopoulos PA, Cheng SC, Wahner Hendrickson AE, Penson RT, Schumer ST, Doyle LA, Lee EK, Kohn EC, Duska LR, Crispens MA, Olawaiye AB, Winer IS, Barroilhet LM, Fu S, McHale MT, Schilder RJ, Färkkilä A, Chowdhury D, Curtis J, Quinn RS, Bowes B, D'Andrea AD, Shapiro GI, Matulonis UA. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020. PubMed
  • Färkkilä A, Gulhan DC, Casado J, Jacobson CA, Nguyen H, Kochupurakkal B, Maliga Z, Yapp C, Chen YA, Schapiro D, Zhou Y, Graham JR, Dezube BJ, Munster P, Santagata S, Garcia E, Rodig S, Lako A, Chowdhury D, Shapiro GI, Matulonis UA, Park PJ, Hautaniemi S, Sorger PK, Swisher EM, D'Andrea AD, Konstantinopoulos PA. Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun 2020; 11:1459. PubMed
  • Kim SH, Da Cruz Paula A, Basili T, Dopeso H, Bi R, Pareja F, da Silva EM, Gularte-Mérida R, Sun Z, Fujisawa S, Smith CG, Ferrando L, Martins Sebastião AP, Bykov Y, Li A, Silveira C, Ashley CW, Stylianou A, Selenica P, Samore WR, Jungbluth AA, Zamarin D, Abu-Rustum NR, Helin K, Soslow RA, Reis-Filho JS, Oliva E, Weigelt B. Identification of recurrent FHL2-GLI2 oncogenic fusion in sclerosing stromal tumors of the ovary. Nat Commun 2020; 11:44. PubMed
  • Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol 2020. PubMed
  • Konstantinopoulos PA, Waggoner S, Vidal GA, Mita M, Moroney JW, Holloway R, Van Le L, Sachdev JC, Chapman-Davis E, Colon-Otero G, Penson RT, Matulonis UA, Kim YB, Moore KN, Swisher EM, Färkkilä A, D'Andrea A, Stringer-Reasor E, Wang J, Buerstatte N, Arora S, Graham JR, Bobilev D, Dezube BJ, Munster P. Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncol 2019. PubMed
  • Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol. 2019; 20:570-580. PubMed
  • Wang S, Blois A, El Rayes T, Liu JF, Hirsch MS, Gravdal K, Palakurthi S, Bielenberg DR, Akslen LA, Drapkin R, Mittal V, Watnick RS. Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. Sci Transl Med 2016; 8:329ra34. 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
  • 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
  • Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol 2014. PubMed
  • Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, Cherniack AD, Ambrogio L, Cibulskis K, Bertelsen B, Romero-Cordoba S, Treviño V, Vazquez-Santillan K, Guadarrama AS, Wright AA, Rosenberg MW, Duke F, Kaplan B, Wang R, Nickerson E, Walline HM, Lawrence MS, Stewart C, Carter SL, McKenna A, Rodriguez-Sanchez IP, Espinosa-Castilla M, Woie K, Bjorge L, Wik E, Halle MK, Hoivik EA, Krakstad C, Gabiño NB, Gómez-Macías GS, Valdez-Chapa LD, Garza-Rodríguez ML, Maytorena G, Vazquez J, Rodea C, Cravioto A, Cortes ML, Greulich H, Crum CP, Neuberg DS, Hidalgo-Miranda A, Escareno CR, Akslen LA, Carey TE, Vintermyr OK, Gabriel SB, Barrera-Saldaña HA, Melendez-Zajgla J, Getz G, Salvesen HB, Meyerson M. Landscape of genomic alterations in cervical carcinomas. Nature 2014; 506:371-5. PubMed
  • Ullal AV, Peterson V, Agasti SS, Tuang S, Juric D, Castro CM, Weissleder R. Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates. Sci Transl Med 2014; 6:219ra9. PubMed
  • Perets R, Wyant GA, Muto KW, Bijron JG, Poole BB, Chin KT, Chen JY, Ohman AW, Stepule CD, Kwak S, Karst AM, Hirsch MS, Setlur SR, Crum CP, Dinulescu DM, Drapkin R. Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. Cancer Cell 2013; 24:751-65. PubMed
Hide
See Program Members See Program Clinical Trials

Ovarian Cancer SPORE

PIs: Alan D'Andrea, MD (DFCI); Ursula Matulonis, MD (DFCI); Cesar M. Castro, MD, MMSc (MGH)

SPORE Projects

ATR inhibitor-mediated reversal of PARP inhibitor resistance in high-grade serous ovarian cancer (HGSOS)
Co-Leaders: Geoffrey Shapiro, MD, PhD (DFCI); David Spriggs, MD (MGH); Lee Zou, PhD (MGH)

Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancer
Co-Leaders: Panagiotis A. Konstantinopoulos MD, PhD (DFCI); Catherine Wu, MD (DFCI)

Evaluation of the Efficacy of Trametinib + Navitoclax in recurrent ovarian carcinoma
Co-Leaders: Joan S. Brugge, Ph.D (HMS); Gad Getz, PhD (MGH); Ursula Matulonis, MD (DFCI)

Visit the Ovarian Cancer SPORE page