NEW YORK (GenomeWeb) – An international research team led by the Baylor Scott & White Research Institute (BSWRI) and Translational Genomics Research Institute (TGen) has begun developing an early detection system for pancreatic cancer after securing a federal grant from the National Cancer Institute.
According to Sunil Sharma, TGen's deputy director of clinical sciences, clinicians currently lack an accurate and effective screening methodology for pancreatic cancer. By the time doctors diagnose the patients with the condition, the disease has metastasized to other parts in the body.
"[Pancreatic cancer] is rapidly increasing in incidence, and there is a huge urgency to develop a screening test," Sharma said. "As the third most common type of cancer, over 20,000 people are diagnosed each year."
With the help of a five-year, $5.1 million grant from the NCI's Pancreatic Cancer Detection Consortium, the collaborators aim to identify high-risk precancerous lesions and early-stage pancreatic cancer in patients who are candidates for surgery or other types of intervention.
According to Ajay Goel, one of the study's principal investigators and director of the Center for Gastrointestinal Research at BSWRI, previous studies have not discovered exclusive liquid biopsy markers for early stage pancreatic cancer. Previous research has only applied known RNA biomarkers in other contexts or cancers by validating them for pancreatic cancer, "instead of discovering comprehensively sequencing-based approaches" for early stage pancreatic cancer. In addition, most teams have focused on biomarkers for advanced stages of pancreatic cancer, which Goel believes is counterintuitive to treatment.
Goel's team at BSWRI will examine a variety of molecular markers including proteins and DNA, while focusing most importantly on microRNAs (miRNAs), which help regulate genes and cancer development. They aim to discover candidate cell-free and exosomal-miRNA biomarkers using whole genome small RNA-Seq in matched tissue and plasma from patients with pancreatic ductal adenocarcinoma (PDAC), precancerous neoplasms (PNs), pancreatitis, and normal pancreas.
Working in tandem with universities and medical centers around the US, South Korea, and Japan, the researchers will have a prospective, diverse biorepository of cancer samples to examine.
"We will perform close to three to four thousand prospective enrollment samples over eight sites in the next five years, which will not only be important for our own projects, but will also become another important resource for other ... investigators on pancreatic cancer," Goel explained.
The researchers will combine the multiple signals into a biomarker panel that distinguishes patients with PDAC from patients with PNs or pancreatitis. While sensitivity is not a problem for the panel because of the multiple copies of RNA that exist in the pancreatic cells, Goel admits that specificity will be a concern with miRNA-based biomarkers.
In order to address the problem, the team will also examine exosomal RNAs in patient samples. The miRNAS can resist nuclease-mediated degradation in tissues, blood, and other body fluids because of their small size and exosome shells.
"We know that the exosomes are produced by epithelial cells from the tumor cells, and their microvesicle membrane carries the cell surface markers from the cell of origin," Goel explained. "We can [then] pull out exosomes from blood by looking at antigens expressed on the cell surface for that particular organ, since we know for sure that they're from the pancreas, and enrich them and open up to see what's inside."
Goel and his team will then attempt to use the panel prospectively to identify groups of patients with PDAC and PNs. Because miRNA expression patterns are highly tissue-specific, they may indicate early malignancies in the organ of origin, even if measured in a patient's bloodstream.
Since the grant approval in September, the consortium has initiated multiple different projects, beginning with the kickoff meeting earlier this month in Phoenix, Arizona. While teams across the eight sites have finished collecting initial cell samples, Sharma said that official RNA-Seq trials will start in early 2018. Goel believes that working with teams at the different universities and cancer centers on different biomarkers will allow true semi-blind validation of biomarkers.
"We already have access to a large quantity of samples," Goel explained. "We plan to perform [sequencing on] three to four thousand samples from patients over the next four to five years."
In addition to searching for early-stage biomarkers for pancreatic cancer, Goel believes that the methodology could be applied to other types of cancer, including esophageal, ovarian, and colorectal cancer (CRC). In the last decade, Goel's team has discovered, validated, published, and patented novel DNA methylation and various non-coding RNA-based biomarkers as potential biomarkers for the early detection of gastrointestinal cancers.
In 2015, Goel and his team at Baylor University published a study that focused on miRNA biomarkers for CRC to determine metastasis risk.
Goel believes the international consortium will produce "promising panels or markers for translational potential to be used in the clinic for commercialization."
The miRNA biomarker panel for pancreatic cancer being developed by Goel's team may eventually produce a non-invasive, early-warning system that will potentially allow clinicians to detect the disease before it metastasizes further into the patient's bloodstream.