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Have We Finally Isolated A Pancreatic Cancer Biomarker?

Unlike some other cancer forms death rates from pancreatic cancer have been continuously raising due to a persistent absence of effective treatments beyond surgery. Inability to screen has also significantly limited progress-making for this tumor type. Typically by the time it’s diagnosed, it has already spread. The prestigious scientific journal Nature reported a new molecular study of pancreatic tumors that exploits the use of liquid biopsies to detect proteins from exosomes, tiny vesicles collected from blood samples of pancreatic cancer patients, bringing new hopes for early diagnosis.

Each year, approximately 49,000 people will receive a diagnosis of pancreatic cancer, and unfortunately the vast majority of them will die from it. Only 7.2 percent of patients with pancreatic cancer are alive 5 years after diagnosis, according to the NCI and only about 15 percent of pancreatic cancer patients can have surgery with curative intent. To make more patients candidates for curative surgery new, reliable diagnostic tools are required. As things stand, there is no screening test available for pancreatic cancer because no clear tumor-specific biomarker has been yet identified. Once the diagnosis and a treatment attempt have been made doctors may require cancer antigen 19-9 (CA19-9) monitoring to follow regression, since CA19-9 levels are expected to fall when the tumor is treated and they may rise again if the disease recurs. However CA19-9 blood levels, according to the American Society of Clinical Oncology cannot be used as a screening test for cancer, particularly pancreatic cancer because the test may be falsely negative in many cases, or abnormally elevated in people who are cancer free (false positive).

A study published in Nature finds a potential new biomarker for prostate cancer that was isolated from exosome circulating in the blood of prostate cancer patients. Exosomes are tiny vesicles particularly enriched in all body fluids that cancerous and non-cancerous cells extrude to send signals or as a waste management system. The investigators collected exosomes from patients and healthy individuals blood samples and grew them in the lab to profile their protein content. Among the 48 proteins specifically found in cancer patient fluids, GPC1 was of particular interest because not only it was unique to cancer exosomes but its levels correlated with the stage of the disease.

To confirm these initial findings, they carried out a perspective study on additional blood samples to see if they could distinguish those from people with and without pancreatic cancer. They reported that all 20 healthy donors examined had low levels of the GPC1-containing exosomes, as did people with non-malignant, inflammatory conditions affecting the pancreas. Five samples taken from people with premalignant pancreatic cancer precursor lesions yielded intermediate levels of the biomarker whereas 56 samples from patients with the most common form of pancreatic cancer, adenocarcinoma, all had high biomarker levels. In pancreatic cancer patients who underwent surgery, the GPC1 marker effectively predicted how long they lived before recurrence of malignancy.

If these findings will be confirmed by other labs, and if the exosome analysis will be adapted to distinguish pancreatic cancer specific markers from those of other types of cancers (some breast cancer patients also scored positive to high levels of blood GPC1), this method could be a life-changer, finally enabling pancreatic cancer screening and improving the monitoring of new drug treatments without the need for invasive procedures or repeated biopsies.

Crown Bioscience has a longstanding research interest in pancreatic cancer. Our pancreatic cancer models are included within our HuPrime® and PDXact collections of patient derived xenografts (PDX), with each model representing the biological characteristics and genetic diversity of the original tumor and patient. Our PDXs can be used to run HuTrials™, Phase II-like mouse avatar trials to identify the responder population before entering late phase human clinical trials. Our HuSignature™, and HuMark™ translational platforms further allow our clients to identify molecular biomarkers and genetic signatures of response before entering the clinic.

Crown Bioscience can be contacted at busdev@crownbio.com for further information on our pancreatic cancer PDX models, our translational platforms or for any other enquiry.

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