An investigational noninvasive exosome-based liquid biopsy shows potential for early detection of pancreatic cancer, an important unmet need, according to research presented at the American Association for Cancer Research (AACR) Annual Meeting 2024.1 When combined with the biomarker CA 19-9, the novel technique detected 97% of stage I and II pancreatic cancers, the investigators said.
“Pancreatic cancer is one of the most fatal malignancies, in large part because the majority of patients are diagnosed only after the cancer has already metastasized,” said senior study author Ajay Goel, PhD, AGAF, Chair of the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope.
“Developing a test that can better detect stage I to II pancreatic cancers is crucial in improving survival rates for this devastating disease. It is of the utmost importance to diagnose patients as early as possible so they have the opportunity to receive potentially curative surgery and treatment,” Dr. Goel told listeners.
Ajay Goel, PhD, AGAF
Caiming Xu, MD, PhD
Initial study author Caiming Xu, MD, PhD, a postdoctoral fellow in Dr. Goel’s group, noted that early detection of pancreatic cancer is challenging, partly because of the nonspecific symptoms of the disease and the location of the pancreas within the abdomen, which makes palpation during a physical exam difficult. Biomarkers such as CA 19-9 are not able to detect early-stage pancreatic cancer when used singly. However, these results suggest they may add to the sensitivity and specificity of the exosome-based liquid biopsy developed by Dr. Goel, Dr. Xu, and colleagues.
The research presented at the AACR Annual Meeting by Dr. Xu focused on the potential of an exosome-based liquid biopsy to detect pancreatic cancer at early stages. The novel approach to liquid biopsy with this test focused on analyzing exosomes; in brief, the function of exosomes is to transport molecular cargo from one cell to another, facilitating intercellular communication. Dr. Xu explained: “Exosomes retain the cytoplasmic content of the cell from which they were shed, essentially replicating the biology of their tissue of origin.”
The team identified eight microRNAs unique to exosomes shed from pancreatic cancer cells. These cells were combined with five cell-free DNA markers found in the blood of patients with pancreatic cancer to develop an associated signature. Previously, the research team analyzed the performance of its exosome-based liquid biopsy signature in a cohort of 95 individuals from the United States or Japan. They were able to detect pancreatic cancer in 98% of cases. The study presented at the AACR Annual Meeting evaluated the performance of the liquid biopsy in large prospective cohorts from multiple institutions and countries.
Study Details and Results
The study included 523 people with pancreatic cancer and 461 healthy donors. These individuals were from the United States (139 with pancreatic cancer, 193 healthy donors); South Korea (184 with pancreatic cancer, 86 healthy donors); Japan (150 with pancreatic cancer, 102 healthy donors); and China (50 with pancreatic cancer, 80 healthy donors).
The cohort from Japan was used as a training and validation set. The signature was able to distinguish with high accuracy between patients with pancreatic cancer vs healthy donors. It was then validated in three independent cohorts from the United States, South Korea, and China. In the U.S. cohort, the diagnostic performance of the signature improved from 91% to 97% when combined with CA 19-9.
“Biomarkers for cancer detection such as CA 19-9 are insufficiently sensitive on their own to detect the presence of pancreatic cancer, but it appears in combination with the signature, the sensitivity is excellent. Our noninvasive, exosome-based diagnostic test caught more pancreatic cancers early, inspiring hope for increasing early detection and treatment of pancreatic cancer,” he noted. Dr. Xu said the test performed with similar accuracy to detect cancers located in the head and tail of the pancreas, two common sites of origin.
Based on the trial results, Dr. Xu suggested this test may be offered to specific groups at greater risk for developing pancreatic cancer. Such groups would include those with new-onset diabetes, benign cysts, chronic pancreatitis, or a family history of pancreatic cancer.
“Our goal is to refine this technique so we can find the earliest signs of pancreatic cancer. We want to find the earliest lead time and see if we can detect the cancer earlier than with radiographic techniques. Perhaps this could be useful in preoperative settings to detect which pancreatic cysts would become problematic later on,” he suggested.
Expert Points of View
Press conference moderator Ryan B. Corcoran, MD, shared the following comments on the exosome-based liquid biopsy for early detection of pancreatic cancer.
Ryan B. Corcoran, MD
“This is a very important area of study and represents an interesting advance. There is a lot of interest in early detection of pancreatic cancer to allow these tests to be used in people without the disease,” he said. “Of course, false-positive results could be a problem, and other challenges would have to be met, but this study shows exciting accuracy rates in [people with] established tumors.” Dr. Corcoran is Co-Chair of the AACR Clinical Trials Program, Director of the Gastrointestinal Cancer Center Program, and Scientific Director of the Termeer Center for Targeted Therapy at the Mass General Cancer Center in Boston.
Dae Won Kim, MD, a gastroenterologist at Moffitt Cancer Center in Tampa, Florida, shared the following thoughts on these study findings: “A majority of patients have advanced and metastatic pancreatic cancers at initial diagnosis, since there are currently no effective screening tests for early detection of pancreatic cancer. An exosome-based liquid biopsy combined with CA 19-9 demonstrated promising results to detect early-stage pancreatic cancer. The liquid biopsy assay detects pancreatic cancer–specific molecules (pancreatic cancer–specific microRNA) in the blood of patients. The assay was tested in more than 500 patients with pancreatic cancer and over 450 healthy donors in multiple countries including the United States. The assay was able to distinguish patients with pancreatic cancer with 88% to 93% accuracy.”
Dr. Kim continued: “This assay may be helpful for early detection of pancreatic cancer in people with high risks, such as a family history of pancreatic cancer, germline BRCA mutations, intraductal papillary mucinous neoplasm (pancreas precancer lesion), or chronic pancreatitis. However, further studies are needed in a larger population before the assay can be used in clinical practice.”
DISCLOSURE: Pharus Diagnostics has a global exclusive license agreement with City of Hope for proprietary biomarkers used in this test. Dr. Goel has served as a consultant to Cellomics and Pharus Diagnostics and is a stockholder and co-founder of Cancer Diagnostics Research Innovation. Dr. Xu reported no conflicts of interest. Dr. Corcoran has served as a consultant or advisor to Alterome Therapeutics, Asana BioSciences, C4 Therapeutics, Coget Biosciences, Erasca, FogPharma, Guardant Health, Interline Therapeutics, Kinnate Biopharma, Mirati Therapeutics, Nested Therapeutics, Pfizer, Qiagen, Remix Therapeutics, Revolution Medicines, Sidewinder Therapeutics, Taiho Pharmaceutical, and Theonys; has received research grants from Eli Lilly, Novartis, and Pfizer; and owns stock in Alterome Therapeutics, Avidity Biosciences, Erasca, Interline Therapeutics, Kinnate Biopharma, Nested Therapeutics, Remix Therapeutics, Revolution Medicine, Sidewinder Therapeutics, and Theonys. Dr. Kim reported no conflicts of interest.
REFERENCE
1. Xu C, et al: AACR Annual Meeting 2024. Abstract 3899. Presented April 8, 2024.
