Caring for Carcinoid Foundation

The Caring for Carcinoid Foundation (CFCF) reports all research progress by our funded scientists. This policy is based on our commitment to transparency and accountability.

CFCF-funded scientists are making rapid progress in unlocking the genetic causes of carcinoid and developing novel, targeted therapies.

We invite you to review their exciting research progress.

Progress Reports
Peer-Reviewed Publications
ASCO Presentations

Developmental Biology (November 2007)

An article entitled "The retinoblastoma protein, RB, is required for gastrointestinal endocrine cells to exit the cell cycle, but not for hormone expression" appeared in the peer-reviewed journal, Developmental Biology. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

The authors are Yang Wang, Subir K. Ray, Philip W. Hinds, and Andrew B. Leiter.

The authors state:

"In summary, our work suggests that RB is important for enteroendocrine cells to undergo cell cycle arrest as they differentiate. However, enteroendocrine cells differentiate to express their characteristic hormones in the absence of functional RB or p107 proteins without exiting the cell cycle. The importance of RB for inducing cell cycle arrest of developing enteroendocrine cells is quite variable between different endocrine lineages and different gastrointestinal organs."

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Clinical Cancer Research (August 2007)

An article entitled, "The Development and Characterization of a Human Midgut Carcinoid Cell Line" appeared in the peer-reviewed journal, Clinical Cancer Research. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

The authors are George Van Buren II, Asif Rashid, Anthony D. Yang, Eddie K. Abdalla, Michael J. Gray, Wenbiao Liu, Ray Somcio, Fan Fan, E. Ramsay Camp, James C. Yao, and Lee M. Ellis.

The authors state:

"Gastrointestinal neuroendocrine tumors (NET) are rare heterogeneous tumors that hypersecrete neuropeptides. The scarcity of good gastrointestinal NET models has limited the ability to study potential therapeutic agents. We describe and characterize the establishment of a human midgut carcinoid tumor cell line carcinoid tumor 2 (CNDT2). ...

The establishment of this human midgut carcinoid tumor cell line may serve as a useful model system for studying cell biology and novel targeted agents in preclinical models."

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Proceedings of the National Academy of Sciences (July 2007)

An article entitled, "Enteroendocrine precursors differentiate independently of Wnt and form serotonin expressing adenomas in response to active B-catenin" appeared in the peer-reviewed journal, Proceedings of the National Academy of Sciences. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

The authors are Yang Wang, Maryann Giel-Moloney, Guido Rindi, and Andrew B. Leiter.

The authors state:

"These results provide direct evidence that some intestinal lineages are specified independently of the Wnt pathway and may lead to a better understanding of the spectrum of neuroendocrine differentiation frequently seen in human gastrointestinal cancer."

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Journal of Clinical Oncology (August 2006)

An article entitled, "Phase II Study of Recombinant Human Endostatin in Patients With Advanced Neuroendocrine Tumors" appeared in the peer-reviewed journal, Journal of Clinical Oncology. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

The authors are Matthew H. Kulke, Emily K. Bergsland, David P. Ryan, Peter C. Enzinger, Thomas J. Lynch, Andrew X. Zhu, Jeffrey A. Meyerhardt, John V. Heymach, William E. Fogler, Carolyn Sidor, Ann Michelini, Kate Kinsella, Alan P. Venook, and Charles S. Fuchs.

The authors conclude:

"Endostatin is a 20-kd proteolytic fragment of collagen XVIII that, in preclinical studies, has been shown to have antiangiogenic and antitumor activity. Both preclinical and human phase I studies of recombinant human endostatin (rhEndostatin) suggested activity in neuroendocrine tumors, which are known to be hypervascular. We therefore performed a multicenter phase II study of rhEndostatin in patients with carcinoid or pancreatic neuroendocrine tumors.

... rhEndostatin was associated with minimal toxicity. However, among 40 patients assessable for radiologic response, none experienced partial response to therapy, as defined by WHO criteria. The median steady-state trough level achieved after dose escalation was 331 ng/mL, within the postulated therapeutic range.

Treatment with rhEndostatin did not result in significant tumor regression in patients with advanced neuroendocrine tumors."

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Digestive Diseases and Sciences (2006)

An article entitled, "Alkaline Phosphatase Predicts Survival in Patients with Metastatic Neuroendocrine Tumors" appeared in the peer-reviewed journal, Digestive Diseases and Sciences. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

The authors are Thomas E. Clancy, MD, Tanya P. Sengupta, Jessica Paulus, Fawzia Ahmed, Mei-Sheng Duh, and Matthew Kulke, MD.

The authors conclude:

"The clinical course of patients with metastatic neuroendocrine tumors is highly variable. While some patients experience an indolent clinical course over many years, other patients may rapidly succumb to their disease. Little is known about prognostic factors in these patients, making decisions regarding their management more difficult.

We performed a retrospective analysis of 137 patients with metastatic neuroendocrine tumors referred to our institution for treatment. Potential prognostic factors were evaluated using multivariate survival analysis. The median overall survival of patients in our cohort was 6.0 years, although the range of survival times was broad (48 days to 23.4 years). Alkaline phosphatase levels above normal were predictive of shorter survival in both univariate and multivariate analysis. Elevated chromogranin A levels were also associated with shorter survival in univariate analysis; in a multivariate analysis, however, this correlation was no longer significant. There was no association between survival and gender, primary tumor site, or presence or absence of carcinoid syndrome. Elevated alkaline phosphatase is a robust adverse prognostic factor for survival in patients with metastatic neuroendocrine tumors and may be superior to chromogranin A in this setting. Close monitoring of alkaline phosphatase levels may be useful when considering initiation or changes of therapy in patients with metastatic neuroendocrine tumors."

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Journal of Clinical Oncology (January 2006)

Dr. Matthew Kulke published clinical trial results in the January 20, 2006 issue of the peer-reviewed journal, Journal of Clinical Oncology. This article recognizes the Caring for Carcinoid Foundation for its research funding support.

Dr. Kulke conducted a Phase II trial to treat neuroendocrine patients with a combination of temozolomide and thalidomide. This drug combination shrank neuroendocrine tumors in 25 percent of the study participants and was biochemically active against tumors in 40 percent of the participants.

In announcing his results, Dr. Kulke said:

"Neuroendocrine tumors are among the most vascular, or blood vessel-filled, tumors that exist, so it made sense to test chemotherapy in combination with an angiogenesis inhibitor like thalidomide, which blocks blood vessel growth. ... In many patients, the therapy produced a significant response, usually with less severe side effects than with older, standard chemotherapy regimens."

In his article, Dr. Kulke states:

"In conclusion, we report that the combination of temozolomide and thalidomide seems to be an active oral regimen for the treatment of metastatic neuroendocrine tumors and represents a reasonable treatment alternative to older, intravenous regimens for this patient population. Our study suggests that this regimen may be more active in pancreatic endocrine tumors than in carcinoid tumors. Further studies to more precisely assess the relative efficacy of this regimen in pancreatic endocrine and carcinoid tumors are warranted, as are studies to assess the relative contributions of temozolomide and thalidomide to the antitumor activity observed with this combination."

Read press release

Read Journal of Clinical Oncology article

ASCO Presentations

2007 ASCO Annual Meeting

At the 2007 ASCO Annual Meeting, researchers delivered several presentations about carcinoid and neuroendocrine tumor research. These presentations included:

James Yao, MD - "Phase II study of RAD001 (everolimus) and depot octreotide (sandostatin LAR) in advanced low grade neuroendocrine carcinoma (LGNET)"
Timothy Hobday, MD - "MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study"
Matthew Kulke, MD - "Prediction of response to temozolomide (TMZ)-based therapy by loss of MGMT expression in patients with advanced neuroendocrine tumors (NET)"

View ASCO presentations

2006 ASCO Annual Meeting

At the 2006 ASCO Annual Meeting, researchers delivered several presentations about carcinoid and neuroendocrine tumor research. These presentations included:

Matthew Kulke, MD - "A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors"
Timothy Hobday, MD - "A phase II trial of gefitinib in patients with progressive metastatic neuroendocrine tumors: A Phase II Consortium study"
James Yao, MD - "Phase II study of RAD001 (everolimus) and depot octreotide (Sandostatin LAR) in patients with advanced low grade neuroendocrine carcinoma"
Carlo Bello, MS - "Analysis of circulating biomarkers of sunitinib malate in patients with unresectable neuroendocrine tumors: VEGF, IL-8, and soluble VEGF receptors 2 and 3"

View Dr. Kulke abstract

View Dr. Kulke presentation poster

View Dr. Hobday abstract

View Dr. Yao abstract

View Bello abstract

2005 ASCO Annual Meeting

Dr. Matthew Kulke recently completed a Phase II study of SU11248 with carcinoid and islet cell patients. SU11248 is a new, targeted drug similar to Gleevec that is being developed by Pfizer. SU11248 targets multiple tyrosine kinase growth signals and acts as an angiogenesis inhibitor.

Dr. Kulke presented his clinical trial results to the 2005 American Society of Clinical Oncology Annual Meeting. Dr. Kulke concluded:

"SU11248 is well tolerated and is associated with modest response rates and a high level of stable disease when used as a single agent in patients with advanced unresectable neuroendocrine tumors. Additional studies to explore the clinical benefit of SU11248 in patients with neuroendocrine tumors are warranted."

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View presentation (video and slides)