November is Pancreatic Cancer Awareness Month, and it’s marked by the publication of important research from the International Cancer Genome Consortium that has identified thousands of genetic mutations associated with the disease. The study was a collaboration among investigators from Australia, Canada, the US, and the UK and was led by Professor Sean Grimmond from the Institute for Molecular Bioscience in Queensland, Australia, and Professor Andrew Biankin from the Kinghorn Cancer Centre at Garvan Institute of Medical Research/St. Vincent’s Hospital in Sydney.
The investigators examined samples from 99 primary, operable, untreated pancreatic ductal adenocarcinomas, which accounts for >90% of pancreatic cancer. This is the first genomic study to report findings from primary pancreatic tumors. Because of the small size of pancreatic tumors, previous studies used only cell lines or tumors transplanted into mice.
In the 99 tumor samples, the investigators detected 2,627 high-confidence mutations, 2,016 of which were nonsilent. The number of mutations detected per patient averaged 26 but ranged from 1 to 116. There were almost 1500 novel mutations, most of which were uncommon.
“We found over 2,000 mutated genes in total, ranging from the KRAS gene, which was mutated in about 90% of samples, to hundreds of gene mutations that were present in only 1% or 2% of tumors,” Professor Grimmon said. “So while tumors may look very similar under the microscope, genetic analysis reveals as many variations in each tumor as there are patients. This demonstrates that so-called ‘pancreatic cancer’ is not one disease, but many, and suggests that people who seemingly have the same cancer might need to be treated quite differently.”
Professor Biankin suggested that these findings may lead to more targeted therapies. “In this study, we found a set of genes, the axon guidance pathway, that is frequently damaged in pancreatic cancer patients and is associated with potentially poorer outcomes for those patients,” he said. “It is a new marker of pancreatic cancer that can be used to direct prognoses and treatments.”
“‘Personalized medicine,’” Professor Biankin said, “where the molecular profile of a patient is matched to the best treatment, is the way the world is moving for many diseases, not just cancer. The challenge now will be moving from population healthcare and a ‘one drug fits all’ model to personalized healthcare. First, we must take the time to develop the necessary genetic knowledge and implement health systems to translate that knowledge effectively.”
Although the lifetime risk of pancreatic cancer is only approximately 1%, it is the 4th leading cause of cancer death and carries a 5-year survival rate of only 5.8%. Its mortality rate has changed little in 30 years. Approximately 44,000 people are diagnosed with pancreatic cancer and more than 37,000 pancreatic cancer deaths occur annually in the US. Pancreatectomy is the single most effective therapy for pancreatic cancer and the only one that offers a chance of cure, but only 20% of patients present with local, non-metastatic disease suitable for resection. Patients who undergo resection and receive adjuvant therapy have a median survival of 12 to 22 months and a 5-year survival rate of 20% to 25%.
Readers, we want to hear from you!
- Will “personalized medicine” transform the treatment of pancreatic cancer?
- Do you think the survival statistics for pancreatic cancer will improve in the next 5 to 10 years?