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The State of The Fight

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The State of the Fight: Pancreatic Cancer

by Richard Posner, Ph.D.

The State of the Fight: Pancreatic Cancer
Richard Posner, Ph.D., is professor in the Clinical Translational Research Division and head of the Systems Biology Unit of the Developmental Therapeutics Program at the Translational Genomics Research Institute in Phoenix.

During the week I graduated from high school, my mother was diagnosed with chronic myelogenous leukemia (CML). Today, patients with CML are treated with imatinib and do remarkably well, but at the time, there was no effective treatment available and my mother passed away three years later. Watching her battle with cancer spurred my interest in medical research. I currently study pancreatic cancer.

Pancreatic cancer is the fourth leading cause of death from cancer in the U.S. It has the highest mortality rate of all major cancers, with the worst one- and five-year survival of any cancer. Upon diagnosis, fewer than 20 percent of patients have localized, potentially curable tumors. Generally, most new cases are advanced with extensive tumor growth, usually due to the lack of symptoms during the early stages of the disease. Warning signs of pancreatic cancer include new-onset diabetes with accompanying weight loss, vague abdominal pain and persistent tiredness and weight loss.

The overall five-year survival rate among patients with pancreatic cancer is less than 5 percent. In 2011, there will be an estimated 44,000 new cases in the United States, and approximately 37,000 patients will die from the disease.

Risk factors include age, medical history and family history. Pancreatic cancer is more common in the elderly than in the young. Smoking also increases one’s risk. Therefore, one of the best ways to prevent pancreatic cancer is to quit smoking. There is also an increased incidence of pancreatic cancer among patients with a history of diabetes or chronic pancreatitis. Finally, there is a genetic component to the disease. Approximately 5 percent to 10 percent of patients with pancreatic cancer have a family history of the disease. People with two first-degree relatives have a twofold to threefold greater risk. Those with mutations in BRCA1 and BRCA2 (genes that encode proteins involved in DNA repair mechanisms) are also at increased risk for pancreatic cancer.

Patients with advanced pancreatic cancer are usually treated with chemotherapy in an effort to improve survival and alleviate symptoms. Gemcitabine has been the standard of care for first-line treatment of patients with advanced pancreatic cancer, but only 18 percent of patients survive for a year on this drug. Better regimens need to be developed.

Our Dream Team is in the process of completing promising clinical trials for patients with metastatic pancreatic cancer, with the ultimate goal of curing pancreatic cancer. We have recently completed a phase 1/2 clinical trial demonstrating the potential clinical efficacy of a two-drug regimen that combines gemcitabine with nab-paclitaxel, a drug that selectively interferes with the cells that support cancer cells. We were very encouraged by the results. Patients in this study had a median survival of 12.2 months, with 48 percent of patients alive after one year and 25 percent alive after two years.

A phase 3 trial of this drug combination is underway. Additionally, we are now enrolling patients in a clinical trial that adds the recently developed Hedgehog inhibitor GDC-0449 to the gemcitabine/nab-paclitaxel regimen. Our hypothesis is that the Hedgehog inhibitor will “cut off the fuel supply” by inhibiting the glutamine metabolism within the tumor.

These trials are for newly diagnosed (untreated) patients with metastatic disease. In an effort to help patients with advanced cancer or those who have received prior therapy, we are conducting a “personalized medicine”-based clinical trial in which therapy is selected based on molecular profiling of patient tumor samples. Patients in this study receive biopsies of a metastatic lesion, which then undergoes genomic analysis. A tumor board consisting of Dream Team physicians and scientists holds weekly meetings to discuss treatment options for each patient.

In conjunction with these clinical trials, we have done a tremendous amount of work profiling patient tumors. We are establishing a database of genomic abnormalities that we observe and their correlation with the clinical history and outcomes of the patients. Other types of cancers share many of the same genetic changes. By making our data available to other researchers, we hope to impact other cancers as well.

In the meantime the best we can do to prevent pancreatic cancer is to educate one another about the risk factors. Although you can’t change some of the risk factors, like age, you can influence others, like smoking.  Make sure to always consult with your doctor if you experience symptoms; pancreatic cancer is often hard to detect, but may be treatable if found in its early stages.

Every two minutes, someone will die of pancreatic cancer. We are working with a great deal of urgency and optimism to improve treatment options for patients and to cure this disease.

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This year, approximately 1.65 million Americans will be diagnosed with cancer and about 585,720 will die of the disease.