The extracellular vesicle GCP1 serves as an indicator for early detection and prognosis assessment in pancreatic cancer chemotherapy, as identified by the Joint Research Team.

Translated by Emily C.
Edited by Yen-Chien, Lai & Elaine Chuang
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In a groundbreaking development, a collaborative research team from National Yang Ming Chiao Tung University (NYCU) and the School of Medicine at National Cheng Kung University (NCKU) has recently published a cutting-edge precision treatment strategy for Pancreatic Ductal Adenocarcinoma (PDAC).

The team utilized extracellular vesicles with dual-targeting capabilities, referred to as dtEV, serving as carriers loaded with multiple effective RNA nucleic acid drugs. This innovative approach precisely targets PDAC, showcasing promising initial results in inhibiting tumor growth and extending survival in animal experiments. The research findings were published in the prestigious journal Nature Communications.

Advancing Precision Medicine: dtEVs and Targeted Therapies

Led by Professor and Yushan Scholar Li James Lee from NYCU's Institute of Biopharmaceutical Sciences, the team collaborated with Professor Chi-Ying F. Huang, a distinguished faculty member at NYCU's Institute of Biopharmaceutical Sciences, and Dr. Yan-Shen Shan, the Dean of the College of Medicine at NCKU, forming a cross-campus research team.

The study introduces a novel precision medical solution that utilizes a "nanopore electroporation technology platform" to transfect specific plasmid DNA into cells, releasing a substantial amount of engineered dtEV.

These dtEVs can carry high doses of therapeutic RNA nucleic acid drugs, with their extracellular vesicle surfaces adorned with artificially modified targeting proteins. These proteins can fuse with tissue-targeting peptides and bind with humanized monoclonal antibodies, achieving precise targeting of PDAC tumor cells and enabling deep penetration into cancer tissues.

The research results indicate that dtEVs carrying therapeutic RNA nucleic acid drugs effectively suppressed PDAC tumors in mice. In experiments involving mouse-derived xenografts (CDX) or patient-derived xenografts (PDX) of pancreatic cancer, the combination of dtEVs with low doses of the chemotherapy drug gemcitabine successfully inhibited large tumors simulating late-stage pancreatic cancer, as well as intra-mouse metastatic lesions. This led to an extended survival period in the animal models.

Industrializing Breakthroughs: Towards Clinical Application

The research team highlights the potential of this treatment method to produce nucleic acid biopharmaceuticals with specific targeting properties, delivering multiple therapeutic RNA drugs to large solid tumors. Currently, the team is actively working on industrializing this research breakthrough, with the goal of clinical application, and is seeking suitable biotech companies for technology transfer.

PDAC, the most common subtype of pancreatic cancer, poses a significant challenge due to its poor treatment outcomes, primarily attributed to the high fibrosis and density of tumors. The presence of multiple gene mutations in pancreatic cancer further complicates the efficacy of single-drug treatments, leading to high recurrence rates. This innovative research offers a new ray of hope for more effective treatment options for pancreatic cancer patients.

Continuing from the collaborative research team's publication in October last year regarding the latest precision treatment strategies for pancreatic ductal adenocarcinoma, on January 10, 2024, a research team composed jointly by National Yang Ming Chiao Tung University, National Cheng Kung University College of Medicine, Keelung Chang Gung Memorial Hospital, Taipei Veterans General Hospital, and the Memorial Sloan Kettering Cancer Center, discovered that the expression of GPC1 in vesicles holds significant potential as an assessment tool for early diagnosis and prognosis evaluation of pancreatic ductal adenocarcinoma.

The characterization of GCP1 within vesicles proves to be a highly promising assessment tool for pancreatic ductal adenocarcinoma.

In this study, the team utilized the Immuno-nanoparticle Liposome Biochip Assay (ILN biochip assay) and identified several potential biomarkers for pancreatic ductal adenocarcinoma. These included GCP1 mRNA expressed in the subpopulation of extracellular vesicles (exosomes) rich in exosomes and the GCP1 membrane protein in the subpopulation of extracellular vesicles rich in microvesicles. Patients with lower levels of tumor-related microvesicular GCP1 membrane protein and exosomal GCP1 mRNA expression before treatment demonstrated longer overall survival periods.

The research team found that the increased expression of specific oncogenes' mRNA and corresponding proteins within extracellular vesicles in the blood has the potential to serve as a tool for early detection and prognosis assessment of pancreatic ductal adenocarcinoma. This study has been published in Advanced Science.