DF/HCC Program Affiliation

Gynecologic Cancer, Co-Leader

DF/HCC Associations

BIDMC, GYN, Clinical Trial Chairs
Member, Center Scientific Council

Research Abstract

I conduct a large clinical and basic research effort designed to improve the therapy of patients with gynecologic malignancies such as epithelial ovarian cancer. We are active in several areas of investigation, including overcoming drug resistance, developing novel inhibitors of angiogenesis, as well as using microarray gene expression profiling in order to better understand the mechanisms of aggressive tumor behavior and resistance to chemotherapy. 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 which 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 a unique gene signature referred to as the OCPP, which is a powerful prognostic tool that is providing insight into the natural history of ovarian cancer. In addition to offerring patients the opportunity to participate in novel clinical trials using conventional cytotoxic agents and well as anti-angiogenesis drugs, we are also working on vaccine-based strategies in an attempt to overcome drug resistance and to eradicate minimal residual disease after completion of first-line chemotherapy. It is hoped that a combination of these approaches will eventually lead to improvements in survival for women with gynecologic malignancies.

Publications

• Cannistra SA.Cancer of the ovary.N Engl J Med 2004 Dec 9;351(24):2519-29.
  15590954
• 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 ca
  15581974
• 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 Dec 1;22(23):4648-58.
  15505275
• Cannistra SA.BRCA-1 in sporadic epithelial ovarian cancer: lessons learned from the genetics of hereditary disease.Clin Cancer Res 2007 Dec 15;13(24):7225-7.
  18094398
• 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 N
  18024865
• 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 Sep;14(3):781-90.
  17914107
• 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
  17506844
• Cannistra SA.Performance of biopsies in clinical research.J Clin Oncol 2007 Apr 10;25(11):1454-5.
  17416872
• Cannistra SA.Gynecologic oncology or medical oncology: what's in a name?.J Clin Oncol 2007 Apr 1;25(10):1157-9.
  17401003
• Cannistra SA.Intraperitoneal chemotherapy comes of age.N Engl J Med 2006 Jan 5;354(1):77-9.
  16394306
• 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 Nov 1;23(31):7911-8.
  16204010
• Berkenblit A, Cannistra SA.Advances in the management of epithelial ovarian cancer.J Reprod Med 2005 Jun;50(6):426-38.
  16050567
• 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 müllerian origin.Gynecol Oncol 2003 Jun;89(3):486-93.
  12798716
• 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
  12743127
• Schumer ST, Cannistra SA.Granulosa cell tumor of the ovary.J Clin Oncol 2003 Mar 15;21(6):1180-9.
  12637488
• 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 Mar 1;20(5):1158-60.
  11870154
• Raffel GD, Gravallese EM, Schwab P, Joseph JT, Cannistra SA.Diagnostic dilemmas in oncology: case 2. Dermatomyositis and ovarian cancer.J Clin Oncol 2001 Dec 1;19(23):4341-3.
  11731518
• 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
  11511919
• 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 Jun
  11395387
• 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 Aug 1;165(3):1705-11.
  10903782
• 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 ep
  10785477
• Strobel T, Cannistra SA.Beta1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro.Gynecol Oncol 1999 Jun;73(3):362-7.
  10366461
• 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 May 1;59(9):2121-6.
  10232598
• Strobel T, Tai YT, Korsmeyer S, Cannistra SA.BAD partly reverses paclitaxel resistance in human ovarian cancer cells.Oncogene 1998 Nov 12;17(19):2419-27.
  9824152
• Cannistra SA, DeFranzo B, Niloff J, Ottensmeir C.Functional heterogeneity of CD44 molecules in ovarian cancer cell lines.Clin Cancer Res 1995 Mar;1(3):333-42.
  9815989
• 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 Nov 1;58(21):4776-81.
  9809975
• 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 Aug;16(8):2583-90.
  9704707
• 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 Aug 31;77(5):741-6.
  9688308
• 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 Jun 12;14(23):2753-8.
  9190890
• 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 Apr 1;57(7):1228-32.
  9102203
• 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 Nov 26;93(24):14094-9.
  8943066
• 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 Aug;74(3):446-52.
  8695362
• Cannistra SA, Niloff JM.Cancer of the uterine cervix.N Engl J Med 1996 Apr 18;334(16):1030-8.
  8598842
• 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 Apr 5;272(5258):123-6.
  8600523
• Abu-Jawdeh GM, Jacobs TW, Niloff J, Cannistra SA.Estrogen receptor expression is a common feature of ovarian borderline tumors.Gynecol Oncol 1996 Feb;60(2):301-7.
  8631556
• 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 Aug;58(2):216-25.
  7542622
• 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 Aug;13(8):1912-21.
  7543560
• 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 Sep;22(10):996-1002.
  7522188
• Cannistra SA.Cancer of the ovary.N Engl J Med 1993 Nov 18;329(21):1550-9.
  8155119
• 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 Aug 15;53(16):3830-8.
  8339295
• 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 C
  8101563