Gynecologic Cancers Investigators Michael J. Birrer, MD, PhD
John O. Schorge, MD
David M. Boruta II, MD
Anne Kathryn Goodman, MD
Marcela G. del Carmen, MD, MPH
Bo R. Rueda, PhD
Carolyn N. Krasner, MD
Debra A. Bell, MD
John Eichorn, MD
Tayyaba Hasan, PhD
Esther Oliva, MD
Richard T. Penson, MD, MRCP
Anthony H. Russell, MD, FACR
Robert H. Young, MD
Collaborative clinical research is carried out within the Harvard system with the collaboration among the divisions of Gynecologic Oncology within the cancer centers of Massachusetts General Hospital, Brigham and Women's Hospital, Dana-Farber Cancer Center, and the Beth Israel Deaconess Medical Center. Beyond Harvard, collaborative clinical trials are conducted nationally in association with the Gynecologic Oncology Group.
Studies of new means of detecting ovarian cancer, understanding the genetic processes in ovarian carcinomatosis, imaging residual cancer in the peritoneal cavity after completion of therapy, and development of biologic therapy for ovarian cancer form the basis for new treatments still in the pipeline. Collaboration with industry has permitted access to experimental therapies and Phase I and II trials, while novel combinations of drugs designed to confound development of drug resistance are in continuing trials for primary post-surgical therapy of epithelial ovarian neoplasms. The center has expanded its clinical capabilities in surgical management of this disease and its recurrence concurrently with the development of new first-line therapies and drugs for the management of recurrent disease.
With the support of the Vincent Obstetrics and Gynecology Service and the Vincent Center for Reproductive Biology the MGH GYN Tissue Repository has been expanded to include the collection of discarded benign and malignant endometrial and cervical tissue, corresponding serum and applicable clinical information. The expanded tissue repository is expected to compliment our growing focus on translational research spearheaded by an active group of the departments clinical fellows, clinicians and basic scientists.
Earlier research in the Center for Gynecologic Oncology demonstrated the prolongation of disease-free survival with cytoreductive surgery for widely metastatic endometrial cancer. Current research builds upon this experience with further retrospective studies of the natural history of treated disease and prospective trials of novel combinations of conventional chemotherapeutic agents. Similarly, studies of the molecular pathogenesis of this disease will be facilitated by expansion of our tumor-banking program.
Cervical cancer is largely preventable through proper screening and therapy of premalignant disease. Yet it is the leading cause of death among women in a large number of developing countries. Clinical research in this disease extends from investigation of the barriers that prevent women from getting access to screening and early therapy to clinical trials of combination chemotherapy for advanced metastatic and recurrent carcinoma. Development of combination chemotherapy with enhanced response rates and decreased toxicity remain a continued goal of this clinical research.
Should enhanced response to treatments of cancer always come at the price of increased toxicity? What motivates patients to seek clinical trials at the beginning and end of cancer treatment? How should physicians communicate risk and benefits to patients when discussing clinical trials? These are a few of many questions being studied in clinical trials in the Center for Gynecologic Oncology. The center continues to expand dramatically with increased recruitment of physicians and nurse practitioners dedicated to methodically improving patients' lives, working collaboratively with research staff and basic scientists to pursue an enlightened course in bringing translational research to clinical reality.
The Role of Alternative and Complementary Therapy in Cancer Care
Several studies have evaluated acupuncture therapy for women with advanced ovarian cancer. One study looked at the improvement of quality of life. A second randomized, single blind study evaluated the effect of acupuncture on white blood cell counts during chemotherapy. Currently at the Massachusetts General Hospital, the Strength and Serenity Center, a virtual center committed to the education of patients, families, and healthcare providers, is developing a clearinghouse of the worlds literature on alternative and complementary therapy in cancer care.
A multi-institutional study has identified a potential personalized treatment target for the most common form of ovarian cancer.
1 Del Carmen MG, Smith Sehdev AE, Fader AN, Zahurak ML, Richardson M, Fruehauf JP, Montz FJ, Bristow RE
Endometriosis-associated ovarian carcinoma: differential expression of vascular endothelial growth factor and estrogen/progesterone receptors.
Cancer. 10/09/2003; 98(8); 1658-63.
2 del Carmen MG, Eisner B, Willet CG, Fuller AF
Intraoperative radiation therapy in the management of gynecologic and genitourinary malignancies.
Surg Oncol Clin N Am. 03/01/2004; 12(4); 1031-42.
3 del Carmen MG, Rizvi I, Chang Y, Moor AC, Oliva E, Sherwood M, Pogue B, Hasan T
Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo.
J Natl Cancer Inst. 10/19/2005; 97(20); 1516-24.
4 Duska LR, Berkowitz R, Matulonis U, Muto M, Goodman A, McIntyre JF, Klein A, Atkinson T, Seiden MV, Campos S
A pilot trial of TAC (paclitaxel, doxorubicin, and carboplatin) chemotherapy with filgastrim (r-metHuG-CSF) support followed by radiotherapy in patients with "high-risk" endometrial cancer.
Gynecol Oncol. 12/15/2004; 96(1); 198-203.
5 Houck K, Avis NE, Gallant JM, Fuller AF, Goodman A
Quality of life in advanced ovarian cancer: identifying specific concerns.
J Palliat Med. 04/29/2005; 2(4); 397-402.
6 Penson RT, Campos SM, Seiden MV, Krasner C, Fuller AF, Goodman A, Roche M, Willman A, Muzikansky A, Matulonis UA,
A phase II study of fixed dose rate gemcitabine in patients with relapsed müllerian tumors.
Int J Gynecol Cancer. 12/13/2005; 15(6); 1035-41.
7 Hamblin MR, Bamberg MP, Miller JL, Hasan T
Cationic photoimmunoconjugates between monoclonal antibodies and hematoporphyrin: selective photodestruction of ovarian cancer cells.
Appl Opt. 02/27/2008; 37(31); 7184-92.
8 Mizukami Y, Jo WS, Duerr EM, Gala M, Li J, Zhang X, Zimmer MA, Iliopoulos O, Zukerberg LR, Kohgo Y, Lynch MP, Rueda BR, Chung DC
Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells.
Nat Med. 09/07/2005; 11(9); 992-7.
9 Renaud EJ, MacLaughlin DT, Oliva E, Rueda BR, Donahoe PK
Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance.
Proc Natl Acad Sci U S A. 01/05/2005; 102(1); 111-6.
10 DeBernardo RL, Littell RD, Luo H, Duska LR, Oliva E, Kirley SD, Lynch MP, Zukerberg LR, Rueda BR
Defining the extent of cables loss in endometrial cancer subtypes and its effectiveness as an inhibitor of cell proliferation in malignant endometrial cells in vitro and in vivo.
Cancer Biol Ther. 04/28/2005; 4(1); 103-7.
11 Kirley SD, Rueda BR, Chung DC, Zukerberg LR
Increased growth rate, delayed senescense and decreased serum dependence characterize cables-deficient cells.
Cancer Biol Ther. 08/12/2005; 4(6); 654-8.
12 Gonzalez RR, Cherfils S, Escobar M, Yoo JH, Carino C, Styer AK, Sullivan BT, Sakamoto H, Olawaiye A, Serikawa T, Lynch MP, Rueda BR
Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2).
J Biol Chem. 09/04/2006; 281(36); 26320-8.
13 Park do Y, Sakamoto H, Kirley SD, Ogino S, Kawasaki T, Kwon E, Mino-Kenudson M, Lauwers GY, Chung DC, Rueda BR, Zukerberg LR
The Cables gene on chromosome 18q is silenced by promoter hypermethylation and allelic loss in human colorectal cancer.
Am J Pathol. 11/05/2007; 171(5); 1509-19.