ARRA Investments in Pancreatic Cancer
Public Health Burden
Pancreatic cancer is the fourth most common cause of cancer death in the United States. Moreover, the incidence of this disease has increased in recent decades. In 2009, it is estimated that more than 42,000 people will be diagnosed with pancreatic cancer and approximately 35,000 will die from it.
The signs and symptoms of pancreatic cancer usually do not present themselves until the disease is at an advanced stage, when surgical removal is no longer possible. Therefore, the development of reliable methods for the early detection and diagnosis of pancreatic cancer are a high priority. Funding made available through ARRA is helping to address this need. For example:
A multi-institutional research team is developing nanoparticles that will circulate in the blood for long periods of time and enable the early detection of pancreatic cancer, improved pancreatic tumor staging at diagnosis, and, eventually, facilitated delivery of chemotherapy drugs to pancreatic cancer cells.
Pancreatic cancer responds poorly to existing therapies, including surgery, chemotherapy, and radiation therapy. Therefore, more-effective treatments for this disease are urgently needed. ARRA funding is supporting the evaluation of new approaches to pancreatic cancer therapy. For example:
A randomized phase II clinical trial, conducted under the Accelerating Clinical Trials of Novel Oncologic Pathways (ACTNOW) program, is testing an agent that targets the Hedgehog signaling pathway in combination with the chemotherapy drug gemcitabine in the treatment of patients with metastatic pancreatic cancer.
In another trial, patients with pancreatic cancer will be randomly assigned to treatment with monthly cycles of a chemotherapy regimen (irinotecan, cisplatin, bleomycin, and mitomycin C) that is designed to induce DNA-strand breaks in tumor cells with or without the addition of the drug olarparib; olarparib inhibits the activity of a protein called PARP1, which helps repair DNA damage; cells that accumulate substantial amounts of DNA damage cannot survive.
Another research project will culminate in a clinical trial testing the targeted drug AZD7762 in combination with gemcitabine chemotherapy and radiation therapy in the treatment of advanced pancreatic cancer; AZD7762 targets a protein called Chk1, which is a regulator of cell proliferation and DNA damage repair; inhibition of Chk1 activity has been shown to increase sensitivity to chemotherapy and radiation therapy.
Identifying the important genomic changes that occur during pancreatic cancer development and progression will advance our understanding of the disease at the molecular level and improve our ability to diagnose, treat, and, hopefully, prevent it. Funding made available through ARRA is directly supporting genomic research related to pancreatic cancer. For example:
A project focused on identifying new sites of somatic (not inherited) mutation and recurrent patterns of somatic mutation in pancreatic cancer in which tumor suppressor genes and genes involved in the maintenance of genomic integrity are inactivated and oncogenes (genes that cause cancer cells to grow) are activated; this research will help identify and better characterize the key signaling pathways that are altered in pancreatic tumorigenesis.
A project aimed at the development of a screening system that will facilitate the identification of genes that cooperate in pancreatic tumor initiation and progression.
A project that will investigate DNA variation in genes related to abnormal glucose metabolism (in particular, insulin, glucose, and lipid metabolism and insulin resistance), which evidence indicates is associated with pancreatic cancer risk; the interaction of DNA variation and factors such as diet, body mass index, diabetes, medication use, and smoking will also be assessed.
The goal of translational research is to eliminate the barriers between basic research and clinical medicine and translate findings from basic research more quickly and efficiently into medical practice. ARRA funding is supporting translational research related to pancreatic cancer. For example:
Research aimed at developing novel chemotherapeutic agents based on sansalvamide A (San A), a depsipeptide antibiotic produced naturally by a marine fungus; preliminary research has shown that some San A derivatives are cytotoxic to pancreatic and colon cancer cells at very low (nanomolar) concentrations.
Research to develop nanoparticles that will deliver tumor suppressor microRNAs to pancreatic cancer stem cells, which constitute the subset of cells in a pancreatic tumor that have the capacity to initiate the growth of new tumors.
-- Multifunctional nanoparticles in diagnosis and therapy of pancreatic cancer -- Prasad, Paras N. (NY)
N01CM62201-9-0-2 -- A Multi-center, double blind, placebo-controlled, randomized phase II of gemcitabine plus GDC-0449 (NSC-747691), a Hh pathway inhibitor, in patients with metastatic pancreatic cancer -- Vokes, Everett E. (IL)
-- Predicting pancreatic cancer responses for a PARP inhibitor-based clinical trial -- Goggins, Michael G. (MD)
-- Gemcitabine-radiation for advanced pancreatic cancer -- Lawrence, Theodore S. (MI)
-- High-throughput analysis of pancreatic mutations -- Kern, Scott E. (MD)
-- Sensitized screen to identify cooperating genes involved in pancreatic cancer -- Buchberg, Arthur M. (PA)
-- Molecular epidemiology of pancreatic cancer -- Holly, Elizabeth A (CA)
-- Conformational-based design and development of antitumor agents -- McAlpine, Shelli R. (CA)
-- Tumor-targeted silencing of BCL-2/BCL-XL by the self-assembled SiRNA-nanovectors -- Xu, Liang (MI)
Page Last Updated on June 30, 2018
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