Research Centers

Gastrointestinal Cancers Clinical Research

The Tucker Gosnell Center for Gastrointestinal Cancers is the first center of excellence in the Harvard system that focuses on integrated multidisciplinary care and research for hepatic and biliary malignancies.

Gastrointestinal Cancers investigators David P. Ryan, MD
Carlos Fernandez-Del Castillo, MD

Jill N. Allen, MD
Ronald Arellano, MD
David L. Berger, MD
Michael A. Blake, MD
Lawrence S. Blaszkowsky, MD
Liliana Bordeianou, MD
Brenna C. Bounds, MD
William R. Brugge, MD
Paul M. Busse, MD, PhD
Daniel C. Chung, MD
Raymond T. Chung, MD
Jeffrey Clark, MD
A. Benedict Cosimi, MD
James C. Cusack, Jr., MD
Nahel Elias, MD
Cristina R. A. Ferrone, MD
David G. Forcione, MD
Debra A Gervais, MD
Peter F. Hahn, MD, PhD
Martin Hertl, MD
Aram F. Hezel, MD
Richard A. Hodin, MD
Theodore S. Hong, MD
Matthew M. Hutter, MD, MPH
Sanjeeva Kalva, MD
Peter B. Kelsey, MD
Eunice L. Kwak, MD, PhD
Gregory Y. Lauwers, MD
James F. Markmann, MD
Mari Mino-Kenduson, MD
Joseph Misdraji, MD
Peter R. Mueller, MD
Sridhar Ramaswamy, MD
David W. Rattner, MD
Dushyant Sahani, MD
Robert H. Schapiro, MD
Paul C. Shellito, MD
Joseph F. Simeone, MD
Kenneth K. Tanabe
Sarah P. Thayer, MD, PhD
Andrew L. Warshaw, MD
Stephan Wicky, MD
Heidi Yeh, MD
Andrew X. Zhu, MD, PhD
Lawrence Zukerberg, M

Research Summary

The center has undergone tremendous growth since its inception in 2003 to its current clinical volume of over 12,000 patient visits per year. In 2007, more than 150 patients were accrued to clinical trials. New faculty have been recruited to meet the demands associated with an increasing number of clinical trials, and a greater complexity of clinical trials. Previously staffed by two full-time medical oncologists in 1998, the Gosnell Center now has five full-time and two part-time medical oncologists. New faculty have also been recruited in radiation and surgical oncology. The Center's physicians play an important role in teaching fellows of Dana-Farber/Partners CancerCare, including the organization of a fellows teaching conference that has been among the highest rated conferences at both Massachusetts General Hospital and Dana-Farber Cancer Institute.

Since 1998, the Gosnell Center has initiated multiple clinical trials along with our colleagues in Dana-Farber/Partners CancerCare. Two regimens (gemcitabine and docetaxel for metastatic pancreatic cancer and gemcitabine/5FU/external beam radiation for locally advanced pancreatic cancer) were deemed extremely relevant and subsequently evaluated by the Cancer and Leukemia Group B in two separate, multicenter trials. Two Tucker Gosnell clinical investigators served as national principal investigators of CALGB studies in the management of colorectal malignancies. Dr. David Ryan was the principal investigator for CALGB 89901, a Phase I trial of 5FU, oxaliplatin, and external beam radiation therapy in rectal cancer. Dr. Jeffrey Clark was the principal investigator of CALGB 89902, a Phase II study of 5FU, leucovorin, oxaliplatin, and trastuzamab in patients with metastatic colon cancer. The rectal cancer regimen now serves as one of the investigational arms of NSABP R-04.

In collaboration with the NCI, investigators at the Cancer Center have also been performing innovative studies in rectal cancer including a Phase I study of preoperative 5FU, bevacizumab, and external beam radiation therapy in locally advanced rectal cancer. In addition to establishing the safety and tolerance of this regimen, multiple correlative studies involving angiogenesis and tumoral blood flow are evaluating mechanisms of action. This study is supported by an R21 grant. Pilot data involving tumoral blood flow, interstitial fluid pressure, and response have been published in Nature Medicine 2004.

In 2003, the Tucker Gosnell Hepatobiliary Cancer Clinic was established with a generous gift by the Gosnell family to the Cancer Center. The Tucker Gosnell Hepatobiliary Cancer Clinic has funded the recruitment of Sridhar Ramaswamy, MD, who has expertise in DNA microarray technology. Dr. Ramaswamy is using genomic tools to study solid tumor metastasis in GI and other solid tumors, with an eye towards developing newer generation diagnostics and therapeutics. The Tucker Gosnell Hepatobiliary Cancer Clinic has solicited for applications for translational research within the field of hepatic and bile duct cancers. Two of these projects have been funded. In the first Gosnell-funded project, Dr. Raymond Chung is using proteomic tools to identify molecular signatures of hepatocellular carcinoma. In the second Gosnell-funded project Dr. Kenneth Tanabe has demonstrated the important role of serum and liver EGF levels in development of hepatocellular carcinoma in patients with cirrhosis, and is now working towards development of agents for chemoprevention trials. The Gosnell Center also funds a research nurse that has been instrumental in establishing a tumor and blood bank for GI cancer patients.

Finally, the creation of this center has also established a base for clinical research for hepatic malignancies; the first Phase II study of epirubicin and thalidomide in hepatocellular carcinoma was completed and presented at the ASCO 2004 Gastrointestinal Cancer Symposium. Dr. Andrew Zhu serves as the director of hepatobiliary research and has conducted a series of studies evaluating antiangiogenesis inhbitors in the treatment of advanced liver and bile duct cancers. Surgical oncologists and transplant surgeons collaborated to conduct a study of safety and efficacy of hyperthermic isolated liver perfusion. And Gosnell investigators also participated in the first study to evaluate the safety and efficacy of multiple infusions of a replication-competent Herpes virus mutant for patients with unresectable colon cancer liver metastases. In addition to this translational research, Dr. Tanabe and Dr. Martin Hertl have developed advanced liver surgery techniques to resect challenging liver tumors, and these include use of veno-veno bypass with liver remnant in situ cooling and replacement of the retrohepatic IVC and "back-bench" liver resections.

The Tucker Gosnell Gastrointestinal Cancer Center is also one of the leading centers in the research and treatment of pancreatic cancers. Dr. Carlos Fernandez del Castillo leads a nationally recognized laboratory and clinical research program which has evaluated new surgical techniques, cystic lesions of the pancreas, and neuroendocrine tumors. Dr Sarah Thayer has investigated the role of the hedgehog pathway in pancreatic carcinogenesis and Dr. Nabeel Bardeesy is a leading authority on pancreatic carcinogenesis.

1 Sequist LV, Joshi VA, Jänne PA, Muzikansky A, Fidias P, Meyerson M, Haber DA, Kucherlapati R, Johnson BE, Lynch TJ
Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing.
Oncologist. 02/07/2007; 1(1); 90-8.

 

2 Sequist LV, Bell DW, Lynch TJ, Haber DA
Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer.
J Clin Oncol. 02/09/2007; 5(5); 587-95.

 

3 Mostoslavsky R, Singh N, Kirillov A, Pelanda R, Cedar H, Chess A, Bergman Y
Kappa chain monoallelic demethylation and the establishment of allelic exclusion.
Genes Dev. 07/27/1998; 12(12); 1801-11.

 

4 Mostoslavsky R, Singh N, Tenzen T, Goldmit M, Gabay C, Elizur S, Qi P, Reubinoff BE, Chess A, Cedar H, Bergman Y
Asynchronous replication and allelic exclusion in the immune system.
Nature. 11/08/2001; 6860(6860); 221-5.

 

5 Mostoslavsky R, Alt FW, Rajewsky K
The lingering enigma of the allelic exclusion mechanism.
Cell. 09/01/2004; 5(5); 539-44.

 

6 Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW
DNA repair, genome stability, and aging.
Cell. 02/28/2005; 4(4); 497-512.

 

7 Chua KF, Mostoslavsky R, Lombard DB, Pang WW, Saito S, Franco S, Kaushal D, Cheng HL, Fischer MR, Stokes N, Murphy MM, Appella E, Alt FW
Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress.
Cell Metab. 08/01/2005; 1(1); 67-76.

 

8 Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW
Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.
Cell. 01/27/2006; 2(2); 315-29.

 

9 Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L
SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells.
Cell. 09/08/2006; 5(5); 941-54.