Photo of Stephen A. Cannistra,  MD

Stephen A. Cannistra, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-1908
Fax: (617) 975-5598


scannist@bidmc.harvard.edu

Stephen A. Cannistra, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Professor, Medicine, Harvard Medical School
  • Attending Physician, Medical Oncology Service, Dana-Farber Cancer Institute
  • Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Clinical Science Coordinating Committee

Research Abstract

The goal of my research and clinical efforts is to improve the therapy of patients with gynecologic malignancies such as epithelial ovarian cancer. Our program conducts several areas of investigation in a variety of relevant areas including drug resistance, angiogenesis, homologous recombination, and immune checkpoint regulation in ovarian cancer. We have discovered that abnormalities in the pathway of programmed cell death, or apoptosis, may explain at least some of the resistance observed with paclitaxel (Taxol TM), one of the most active agents used in the treatment of patients with this disease. Specifically, we have observed that tumor cells that lack expression of the BAX pro-apoptotic protein are relatively resistant to paclitaxel, both in vitro and in the clinic, and that low levels of BAX predict for inferior response rates and disease-free survivals. By using microarray technology, we have identified unique gene signatures that may have important prognostic value, as well as predictive value in identifying patients more likely to response to PARP inhibitors. Through our clinical investigation efforts we have defined an important role for anti-angiogenic therapy in ovarian cancer treatment (bevacizumab) and have expanded these observations by developing preclinical models that allow us to better understand the anti-angiogenic potential of thrombospondin derivatives in this disease. Finally, we have been investigating the pathways involved in immune checkpoint regulation, specifically related to PD-L1 expression in ovarian cancer, in order to better predict which patients may benefit from therapies that specifically interfere with this process (such as antibodies against CTLA-4, PD-1, and PD-L1). It is hoped that a combination of these approaches will eventually lead to improvements in survival for women with gynecologic malignancies.

Publications

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  • Liu JF, Cannistra SA. Emerging role for bevacizumab in combination with chemotherapy for patients with platinum-resistant ovarian cancer. J Clin Oncol 2014; 32:1287-9. PubMed
  • Goodwin PJ, Ballman KV, Small EJ, Cannistra SA. Evaluation of treatment benefit in Journal of Clinical Oncology. J Clin Oncol 2013; 31:1123-4. PubMed
  • Haller DG, Cannistra SA. Providing protocol information for journal of clinical oncology readers: what practicing clinicians need to know. J Clin Oncol 2011; 29:1091. PubMed
  • Verweij J, Disis ML, Cannistra SA. Phase I studies of drug combinations. J Clin Oncol 2010; 28:4545-6. 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
  • Cannistra SA. Evaluating New Regimens in Recurrent Ovarian Cancer: How Much Evidence Is Good Enough? J Clin Oncol 2010; 28:3101-3. PubMed
  • Penson RT, Dizon DS, Cannistra SA, Roche MR, Krasner CN, Berlin ST, Horowitz NS, Disilvestro PA, Matulonis UA, Lee H, King MA, Campos SM. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 2009; 28:154-9. PubMed
  • Matulonis UA, Berlin S, Ivy P, Tyburski K, Krasner C, Zarwan C, Berkenblit A, Campos S, Horowitz N, Cannistra SA, Lee H, Lee J, Roche M, Hill M, Whalen C, Sullivan L, Tran C, Humphreys BD, Penson RT. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 2009; 27:5601-6. PubMed
  • Cannistra SA. Phase II Trials in Journal of Clinical Oncology. J Clin Oncol 2009; 27:3073-6. PubMed
  • Konstantinopoulos PA, Spentzos D, Cannistra SA. Gene-expression profiling in epithelial ovarian cancer. Nat Clin Pract Oncol 2008; 5:577-87. PubMed
  • Cannistra SA. Challenges and pitfalls of combining targeted agents in phase I studies. J Clin Oncol 2008; 26:3665-7. PubMed
  • Comander AH, Cannistra SA. A feasibility study of low-dose, prolonged oral topotecan in patients with advanced ovarian, fallopian tube, or primary peritoneal serous cancer who have attained a complete clinical response following platinum-based chemotherapy. Int J Gynecol Cancer 2007; 18:51-8. 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
  • Cannistra SA. BRCA-1 in sporadic epithelial ovarian cancer: lessons learned from the genetics of hereditary disease. Clin Cancer Res 2007; 13:7225-7. PubMed
  • Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25:5180-6. PubMed
  • Spentzos D, Cannistra SA, Grall F, Levine DA, Pillay K, Libermann TA, Mantzoros CS. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocr Relat Cancer 2007; 14:781-90. PubMed
  • Cannistra SA. Performance of biopsies in clinical research. J Clin Oncol 2007; 25:1454-5. PubMed
  • Cannistra SA. Gynecologic oncology or medical oncology: what's in a name? J Clin Oncol 2007; 25:1157-9. PubMed
  • Cannistra SA. Intraperitoneal chemotherapy comes of age. N Engl J Med 2006; 354:77-9. PubMed
  • Spentzos D, Levine DA, Kolia S, Otu H, Boyd J, Libermann TA, Cannistra SA. Unique gene expression profile based on pathologic response in epithelial ovarian cancer. J Clin Oncol 2005; 23:7911-8. PubMed
  • Berkenblit A, Cannistra SA. Advances in the management of epithelial ovarian cancer. J Reprod Med 2005; 50:426-38. PubMed
  • Cannistra SA. Cancer of the ovary. N Engl J Med 2004; 351:2519-29. PubMed
  • Spentzos D, Levine DA, Ramoni MF, Joseph M, Gu X, Boyd J, Libermann TA, Cannistra SA. Gene expression signature with independent prognostic significance in epithelial ovarian cancer. J Clin Oncol 2004; 22:4648-58. PubMed
  • Berkenblit A, Seiden MV, Matulonis UA, Penson RT, Krasner CN, Roche M, Mezzetti L, Atkinson T, Cannistra SA. A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer. Gynecol Oncol 2004; 95:624-31. PubMed
  • Berkenblit A, Tung N, Kim Y, Feyler H, Niloff J, Berghe KV, Cannistra SA. Phase I trial of docetaxel, carboplatin, and gemcitabine as first-line therapy for patients with high-risk epithelial tumors of mlerian origin. Gynecol Oncol 2003; 89:486-93. PubMed
  • Cannistra SA, Bast RC, Berek JS, Bookman MA, Crum CP, DePriest PD, Garber JE, Koh WJ, Markman M, McGuire WP, Rose PG, Rowinsky EK, Rustin GJ, Skates SJ, Vasey PA, King L. Progress in the management of gynecologic cancer: consensus summary statement. J Clin Oncol 2003; 21:129-32. PubMed
  • Schumer ST, Cannistra SA. Granulosa cell tumor of the ovary. J Clin Oncol 2003; 21:1180-9. PubMed
  • Cannistra SA. Is there a "best" choice of second-line agent in the treatment of recurrent, potentially platinum-sensitive ovarian cancer? J Clin Oncol 2002; 20:1158-60. PubMed
  • Raffel GD, Gravallese EM, Schwab P, Joseph JT, Cannistra SA. Diagnostic dilemmas in oncology: case 2. Dermatomyositis and ovarian cancer. J Clin Oncol 2001; 19:4341-3. PubMed
  • Smith WM, Zhou XP, Kurose K, Gao X, Latif F, Kroll T, Sugano K, Cannistra SA, Clinton SK, Maher ER, Prior TW, Eng C. Opposite association of two PPARG variants with cancer: overrepresentation of H449H in endometrial carcinoma cases and underrepresentation of P12A in renal cell carcinoma cases. Hum Genet 2001; 109:146-51. PubMed
  • Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 2001; 158:2097-106. PubMed
  • Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D, Kufe D. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 2000; 165:1705-11. PubMed
  • Tung N, Berkowitz R, Matulonis U, Quartulli M, Seiden M, Kim Y, Niloff J, Cannistra SA. Phase I trial of carboplatin, paclitaxel, etoposide, and cyclophosphamide with granulocyte colony stimulating factor as first-line therapy for patients with advanced epithelial ovarian cancer. Gynecol Oncol 2000; 77:271-7. PubMed
  • Christina Herold and Stephen A. Cannistra. Gynecologic Cancer. In: Dale DC, Federman DD, ed. American College of Physicians (ACP) Medicine, 2013 edition Scientific American Medicine. 2014.
  • Cannistra SA, Gershenson DM, Recht A. Ovarian Cancer, Peritoneal Carcinoma, and Fallopian Tube Carcinoma 2014.
  • Joyce Liu and Stephen A. Cannistra. Emerging Role for Bevacizumab in Combination with Chemotherapy for Patients with Platinum-Resistant Ovarian Cancer 2014.
  • Strobel T, Cannistra SA. Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro. Gynecol Oncol 1999; 73:362-7. PubMed
  • Tai YT, Strobel T, Kufe D, Cannistra SA. In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene. Cancer Res 1999; 59:2121-6. PubMed
  • Strobel T, Tai YT, Korsmeyer S, Cannistra SA. BAD partly reverses paclitaxel resistance in human ovarian cancer cells. Oncogene 1998; 17:2419-27. PubMed
  • Strobel T, Kraeft SK, Chen LB, Cannistra SA. BAX expression is associated with enhanced intracellular accumulation of paclitaxel: a novel role for BAX during chemotherapy-induced cell death. Cancer Res 1998; 58:4776-81. PubMed
  • Fink D, Nebel S, Norris PS, Baergen RN, Wilczynski SP, Costa MJ, Haas M, Cannistra SA, Howell SB. Enrichment for DNA mismatch repair-deficient cells during treatment with cisplatin. Int J Cancer 1998; 77:741-6. PubMed
  • Tai YT, Lee S, Niloff E, Weisman C, Strobel T, Cannistra SA. BAX protein expression and clinical outcome in epithelial ovarian cancer. J Clin Oncol 1998; 16:2583-90. PubMed
  • Strobel T, Swanson L, Korsmeyer S, Cannistra SA. Radiation-induced apoptosis is not enhanced by expression of either p53 or BAX in SW626 ovarian cancer cells. Oncogene 1997; 14:2753-8. PubMed
  • Strobel T, Swanson L, Cannistra SA. In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: a novel role for CD44 in the process of peritoneal implantation. Cancer Res 1997; 57:1228-32. PubMed
  • Strobel T, Swanson L, Korsmeyer S, Cannistra SA. BAX enhances paclitaxel-induced apoptosis through a p53-independent pathway. Proc Natl Acad Sci U S A 1996; 93:14094-9. PubMed
  • Ottensmeier C, Swanson L, Strobel T, Druker B, Niloff J, Cannistra SA. Absence of constitutive EGF receptor activation in ovarian cancer cell lines. Br J Cancer 1996; 74:446-52. PubMed
  • Cannistra SA, Niloff JM. Cancer of the uterine cervix. N Engl J Med 1996; 334:1030-8. PubMed
  • Scully R, Ganesan S, Brown M, De Caprio JA, Cannistra SA, Feunteun J, Schnitt S, Livingston DM. Location of BRCA1 in human breast and ovarian cancer cells. Science 1996; 272:123-6. PubMed
  • Abu-Jawdeh GM, Jacobs TW, Niloff J, Cannistra SA. Estrogen receptor expression is a common feature of ovarian borderline tumors. Gynecol Oncol 1996; 60:301-7. PubMed
  • Cannistra SA, Abu-Jawdeh G, Niloff J, Strobel T, Swanson L, Andersen J, Ottensmeier C. CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors. J Clin Oncol 1995; 13:1912-21. PubMed
  • Cannistra SA, Ottensmeier C, Niloff J, Orta B, DiCarlo J. Expression and function of beta 1 and alpha v beta 3 integrins in ovarian cancer. Gynecol Oncol 1995; 58:216-25. PubMed
  • Cannistra SA, DeFranzo B, Niloff J, Ottensmeir C. Functional heterogeneity of CD44 molecules in ovarian cancer cell lines. Clin Cancer Res 1998; 1:333-42. PubMed
  • Cannistra SA, Ottensmeier C, Tidy J, DeFranzo B. Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. Exp Hematol 1994; 22:996-1002. PubMed
  • Cannistra SA. Cancer of the ovary. N Engl J Med 1993; 329:1550-9. PubMed
  • Cannistra SA, Kansas GS, Niloff J, DeFranzo B, Kim Y, Ottensmeier C. Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44H. Cancer Res 1993; 53:3830-8. PubMed
  • Tepler I, Cannistra SA, Frei E, Gonin R, Anderson KC, Demetri G, Niloff J, Goodman H, Muntz H, Muto M. Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy. J Clin Oncol 1993; 11:1583-91. PubMed
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