Dream Team plans to stop pancreatic cancer before symptoms occur

Deeply entrenched and mature by the time it's found, pancreatic cancer is one of the hardest to defeat. A Dream Team assembled by Stand Up to Cancer and led by an investigator at The University of Texas MD Anderson Cancer Center will test new ways to find the disease in its emerging, more vulnerable phase in people who are at high risk for developing it.

"Our plan is to intercept pancreatic cancer by finding it and stopping it before symptoms occur, when the disease is still silent or, even better, before it's actually cancer," said principal investigator Anirban Maitra, M.B.B.S., scientific director of the Sheikh Ahmed Pancreatic Cancer Research Center at MD Anderson.

The team will deploy universal testing for inherited mutations in pancreatic cancer patients, apply deep machine learning to improve imaging, tailor vaccines to knock down emerging disease and sift the best ideas to develop blood tests for predicting risk and detecting precursor or early disease.

Co-leaders of the SU2C-Lustgarten Foundation Pancreatic Cancer Interception Dream Team: Intercepting Pancreatic Cancer in High-Risk Cohorts are Michael Goggins, M.D., professor of pathology, medicine and oncology, Johns Hopkins University, Baltimore; and Scott Lippman, M.D., director of Moores Cancer Center, University of California San Diego Health. Other participating institutions are the Dana-Farber Cancer Institute in Boston, the Massachusetts Institute of Technology and Mayo Clinic.

About 53,670 people will receive a diagnosis of pancreatic cancer in 2017, and about 43,090 will die of the disease, according to the American Cancer Society. Pancreatic cancer accounts for about 3 percent of U.S. cancers but 7 percent of deaths caused by cancer. About 8 percent of patients survive to five years.

The $7 million grant over four years is one of four announced by Stand Up to Cancer in conjunction with various collaborators, including the Lustgarden Foundation for Pancreatic Cancer Research.

Maitra, who also is co-leader of the Pancreatic Cancer Moon Shot™, part of MD Anderson's Moon Shots Program™ to accelerate the development of new approaches based on scientific discoveries to prevent, detect and treat cancer, said there are four projects for the Dream Team.

Using genomic testing to identify those at risk

The overall idea is to take advantage of known risk factors such as germline mutations (inherited abnormalities of DNA) that are known to raise pancreatic cancer risk.

The first step will be to use a sequencing technique from Color Genomics to test the germline DNA of 2,000 consecutive pancreatic cancer patients, in order to identify those with known risk-raising mutations, such as BRCA1 and BRCA2. About 12 percent of all patients carry such mutations.

First-degree relatives of patients who are found to have mutations will then be offered genetic counseling and screening through high-risk clinics, such as the one directed by Florencia McAllister, M.D., assistant professor of Clinical Cancer Prevention through the Pancreatic Cancer Moon Shot at MD Anderson. Those relatives who have mutations will enter an active screening protocol, which includes serial imaging and blood-based biomarker testing.

Machine learning to improve imaging

"If somebody does have silent disease, current CT and MRI scans are woefully inadequate in picking up the small tumors we want to detect," Maitra said. The team will apply computational algorithms to teach computers to recognize pancreatic abnormalities that now escape the human eye, Maitra said.

The goal is to create software packages that could be shared with other institutions. "We're taking standard-of-care imaging but enhancing it with computational algorithms," Maitra said.

Vaccines to intercept disease

Currently cancer-free individuals identified as high-risk due to the presence of germline mutations, who also have pre-cancerous lesions such as cysts on their pancreas, will be enrolled in the first ever vaccine trial to prevent pancreatic cancer.

"Right now, such individuals are followed with endoscopy and periodic imaging, and you hope to catch any progression to cancer early, but there's no active interception to be done for them," Maitra said.

The vaccine, unlike other cancer therapies, is a low-impact treatment that the researchers think is well-suited for interception.

Biomarkers to clarify risk

Molecular biomarkers can be used to identify manifest pancreatic cancer, Maitra said, but "they're awful at detecting occult (silent) disease."

The Dream Team will bring together leaders in the field of biomarker research to test the best biomarker candidates in hundreds of blood samples gathered in a variety of research cohorts that tracked people over time. A fraction of these otherwise healthy people enrolled in longitudinal studies developed pancreatic cancer.

"Something in that person placed him or her at very high risk for pancreatic cancer," Maitra said. Identifying biomarkers in that group can help guide future selection of people who should have more intense screening or early treatment.

Stand Up to Cancer, a division of the Entertainment Industry Foundation, raises funds to accelerate the pace of research to get new therapies to cancer patients quickly by funding teams of top researchers across multiple institutions to collaborate on vital projects.

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