Caring for Carcinoid Foundation-Funded Researchers Illuminate Genetic Code for a Form of Pancreatic Cancer

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Jan 20, 2011, 02:30 ET

BOSTON, Jan. 20, 2011 /PRNewswire-USNewswire/ -- Through a grant provided by the Caring for Carcinoid Foundation (www.caringforcarcinoid.org), researchers at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center have discovered several key mutations in pancreatic neuroendocrine tumors. This significant finding holds the promise of improving patient diagnosis and treatment and brings the neuroendocrine cancer community closer to a cure. Neuroendocrine cancers affect approximately 100,000 patients in the United States, including, according to published reports, Steve Jobs, CEO of Apple Inc.

Dr. Nickolas Papadopoulos, Ph.D., associate professor at Johns Hopkins Kimmel Cancer Center and lead researcher on this project recognized the support of the Caring for Carcinoid Foundation. "We are very grateful to the Foundation for funding this research. Without their visionary support, this project would not have been possible. We look forward to continuing our work to advance treatment options for neuroendocrine cancer patients," says Dr. Papadopoulos.

Papadopoulos and his team uncovered the set of genetic alterations present among patients with non-functional pancreatic neuroendocrine tumors. They also uncovered a prognostic set of mutations and a rapid way of prioritizing patients for treatments with mTOR inhibiting drugs.

Papadopoulos says, "One of the most significant things we have learned is that each patient with this form of pancreatic cancer has a unique genetic code that predicts how aggressive the disease is and how sensitive it is to specific treatments." Dr. Papadopoulos and his team found that in patients with non-functional pancreatic neuroendocrine tumors, those with specific mutations lived at least 10 years from diagnosis, while more than 60% of patients without these mutations died within five years of diagnosis.

These findings, published online in Science Express on January 20, 2011, suggest new approaches for treating patients with pancreatic neuroendocrine tumors. With few treatment options currently available for pancreatic neuroendocrine tumor patients, these findings represent important advances toward improving treatment options for these patients.

Of these breakthroughs, CFCF Founder and metastatic carcinoid cancer survivor Nancy Lindholm says, "This research finding represents a monumental leap forward in understanding the underlying mechanism of neuroendocrine cancer. Thanks to the phenomenal work of Dr. Papadopoulos and his team, we are one step closer to a cure. I am grateful to the commitment and dedication of the Caring for Carcinoid Foundation community for supporting researchers like Dr. Papadopoulos and making these insights possible. I hope this news brings reviewed optimism and courage to everyone living with carcinoid, pancreatic neuroendocrine, and related neuroendocrine cancers."

The significant findings of Papadopoulos and his team lays the framework for further genomic and drug pathway studies, and visibly demonstrates the progress that is possible through funded research of rare cancers.

About the Caring for Carcinoid Foundation

The Caring for Carcinoid Foundation (CFCF) is dedicated to discovering cures for carcinoid cancer, pancreatic neuroendocrine (also known as islet cell) cancer, and related neuroendocrine cancers. Along with its focus on research, CFCF is committed to supporting patients, families, friends, and caregivers by providing them with complete and up-to-date information. CFCF directs 100 percent of all individual donations to breakthrough scientific research. This is made possible by the generous support of CFCF's board of directors, corporate sponsors and pro bono legal counsel, Proskauer Rose LLP. Since its inception, CFCF has awarded more than 6 million dollars in research grants to leading scientists at renowned institutions worldwide. For more information about CFCF or to support this research, please visit http://www.caringforcarcinoid.org/ or call 617 848 3977 and ask to speak with Executive Director, Lauren Erb.

About Pancreatic Neuroendocrine and related Neuroendocrine Cancers

Neuroendocrine tumors are a type of cancer that can originate almost anywhere in the body. The most common sites from which neuroendocrine tumors arise are the lungs, appendix, small intestine, rectum, and pancreas. Neuroendocrine tumors that arise in the pancreas are called "pancreatic neuroendocrine tumors," "islet cell tumors," or "pancreatic endocrine tumors." According to published news reports, this is the type of cancer Steve Jobs was diagnosed with in 2004. When neuroendocrine tumors originate in other areas, they are most commonly classified as "carcinoid cancer." Currently, between 11,000 and 12,000 new cases of carcinoid cancer are diagnosed each year in the United States, but the number has been increasing by six percent annually.

Summary of Research Findings

Dr. Papadopoulos and his team sequenced the protein coding genes from 10 non-functional pancreatic neuroendocrine tumors and compared these genes' sequences to genes from normal tissue from the same patients to identify the specific genes that were most frequently mutated. Next they checked for these mutations in 58 additional non-functional pancreatic neuroendocrine tumors to understand how frequently the mutations occurred. Frequent mutations were observed in the MEN-1, DAXX, and ATRX genes. While mutations in MEN-1 have been previously associated with other cancers including familial pancreatic neuroendocrine cancer, mutations in DAXX and ATRX have not previously been associated with cancer. This study, for the first time, presents DAXX and ATRX as new targets for pancreatic neuroendocrine cancer therapy and suggests a novel approach to neuroendocrine cancer treatment and diagnostics by targeting epigenetic processes.

While genes contain the instructions for assembling proteins, through epigenetic regulation, cells are able to control whether or not those proteins are actually produced. When epigenetic regulation malfunctions, it can lead to the inactivation of a cancer-suppressing gene, or activation of a cancer-driving gene. This finding indicates that malfunctioning epigenetic regulation may be caused by genetic changes in specific genes and may be important for the development of neuroendocrine cancer, and, therefore, could suggest a new, rational approach to neuroendocrine cancer treatment by targeting epigenetic processes.

Dr. Papadopoulos and his team found that in patients with non-functional pancreatic neuroendocrine tumors, those with mutations in MEN-1, DAXX, and ATRX lived at least 10 years from diagnosis, while more than 60% of patients without these mutations died within five years of diagnosis.

Finally, this study presents a rapid way of prioritizing patients for treatment with mTOR inhibiting drugs such as everolimus and temsirolimus. Fourteen percent of tumor samples contained mutations in the mTOR gene family which regulates cell signaling processes. According to Papadopoulos, "Patients with mutations in the mTOR pathway could be identified for treatment with mTOR inhibiting drugs currently in clinical development."

Link to abstract: http://www.sciencemag.org/content/early/2011/01/19/science.1200609

SOURCE Caring for Carcinoid Foundation