Researchers at Osaka University in Japan have made an exciting breakthrough in the fight against pancreatic ductal adenocarcinoma (PDAC), one of the deadliest forms of cancer. By utilizing a combination of diagnostics and therapeutics, known as ‘theranostics’, the researchers have developed a strategy to detect and destroy this particularly aggressive form of pancreatic cancer. This groundbreaking approach could potentially lead to earlier detection and more effective treatment of the disease, which currently has an average five-year survival rate of less than 10%.
Pancreatic cancer, especially PDAC, is notoriously challenging to detect using conventional imaging methods such as positron emission tomography (PET) scans. However, the research team at Osaka University has developed a process that uses radioactive monoclonal antibodies (mAb) to target a protein called glypican-1 (GPC1), which is highly expressed in PDAC tumors.
GPC1 has been implicated in various aspects of cancer progression, including cell proliferation, invasion, and metastasis. High levels of GPC1 expression often indicate a poor prognosis in certain cancers, including pancreatic cancer. The researchers chose to target GPC1 due to its overexpression in PDAC, while being present in low levels in normal tissues, as explained by Tadashi Watabe, the lead author of the study.
To test their approach, the researchers injected human pancreatic cancer cells into mice and allowed them to develop into tumors. The mice were then administered GPC1 mAb labeled with radioactive zirconium (89Zr) and observed for antitumor effects. Through positron emission tomography (PET) scanning, the researchers confirmed the strong uptake of the mAb into the tumors, indicating potential support for tumor visualization. They also discovered that this uptake was specifically due to the binding of the mAb to GPC1, as mice lacking GPC1 expression displayed significantly less uptake.
Once the tumors were visualized, the researchers administered GPC1 mAb labeled with radioactive astatine (211At), a form of targeted alpha therapy. Alpha therapy involves selectively delivering radioisotopes, in this case, astatine, to cancer cells using mAb or peptides. The radioisotope undergoes alpha decay, delivering kinetic energy that causes irreparable damage to the cells.
The delivery of 211At-GPC1 mAb resulted in DNA double-strand breaks in the cancer cells and significantly reduced tumor growth. The researchers confirmed that these antitumor effects were only observed when mAb internalization was not blocked, and non-radiolabeled GPC1 mAb did not induce the same effects.
“We are encouraged by the promising results of both radiolabeled versions of the GPC1 mAb that we examined,” said Watabe. “89Zr-GPC1 mAb showed high tumoral uptake, while 211At-GPC1 mAb could be used for targeted alpha therapy to support the suppression of PDAC tumor growth.”
The researchers believe that their findings showcase the potential of the theranostics approach in treating PDAC, potentially leading to earlier detection and more effective treatment options in the future. This innovative combination of diagnostics and therapeutics could revolutionize cancer treatment, offering new hope and improved outcomes for patients with pancreatic cancer.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
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