Classifying pancreatic tumors

Pancreatic cancer cells grown in culture. Anne Weston, London Research Institute, Cancer Research UK (image available under a Creative Commons attribution, noncommercial, no derivatives license) 

Pancreatic cancer is like a killer lurking in the shadows. The disease spreads aggressively during early stages without causing specific symptoms.

Every year in the U.S., about 50,000 people are diagnosed with pancreatic cancer. Most are diagnosed at advanced stages when even surgical removal of the cancer may prove to be ineffective.

About 80 percent of patients will die within a year after diagnosis, and only 6 percent will survive beyond five years.

November is pancreatic cancer awareness month, highlighting the urgent need for better diagnosis and treatment methods for the disease.

How does pancreatic cancer develop?

The most common form of pancreatic cancer affects the exocrine tissue, which produces digestive enzymes. These exocrine tumors are called pancreatic adenocarcinoma, or PDA. PDA develops either from pre-cancerous microscopic lesions or from larger, fluid-filled pancreatic cysts that can be seen on abdominal imaging studies. In most cases, the lesions are not detected, because they do not cause any symptoms. If detected early, the lesions can be cured.

What are the risk factors and symptoms?

Risk factors for pancreatic cancer include family history, smoking and certain occupational exposures to dyes and pesticides. Common symptoms include profound weight loss, jaundice (which can also cause itching), nausea, appetite loss, abdominal pain and back pain.

What are the latest research developments?

Identifying heterogeneity in PDA tumors is an important step toward developing more targeted treatments. Jen Jen Yeh and colleagues at the University of North Carolina are working on classifying PDA into subtypes based on the molecular characteristics of the stroma, the dense tissue surrounding the cancerous tissue. Using mathematical approaches and gene-expression analysis, the researchers identified two distinct stromal types among PDA tumor samples — normal and activated. The activated stromal type had higher expression of tumor-promoting genes and was linked to poor survival outcomes in patients with PDA.

Other researchers are looking at whole genomes to classify PDA. Sean Grimmond and colleagues at the University of Queensland, Australia, performed whole-genome sequencing in PDA tumor samples to assess variations in chromosomal structure that disrupt gene function. They classified the tumors into four subtypes: stable, locally rearranged, scattered and unstable. Notably, the unstable tumors consisted of more than 200 structural variations, which primarily disrupted genes related to DNA repair. As these unstable tumors lack proper DNA-repair mechanisms, they respond better to treatments like platinum-based chemotherapy, which kills cancer cells by causing excessive DNA damage.

Indumathi Sridharan Indumathi Sridharan earned her bachelor’s degree in bioinformatics in India. She holds a Ph.D. in molecular biochemistry from Illinois Institute of Technology, Chicago. She did her postdoctoral work in bionanotechnology at Northwestern University.