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Researchers from LABMED has developed a unique 3D model system that can potentially predict drug response in patients with operable pancreatic cancer

Researchers from the laboratory of Mikael Björnstedt from the Division of Pathology, Department of Laboratory Medicine, KI and collaborators have developed a model system which could lead to new and improved treatment for pancreatic ductal adenocarcinoma, one of the major subtypes of pancreatic cancer.

Picture of Carlos F MoroPancreatic cancer is one of the deadliest forms of cancer. Current estimates suggest that only five out of 100 patients survive for 5 years. The prognosis is even worse in the advanced disease, in which cancer cells from primary tumor spread to the other parts of the body, a process known as ‘metastasis’.

Decades old cancer drugs are still in the mainstay for the treatment of pancreatic cancer. Lack of pertinent ‘model systems’ is often attributed as one of the key bottlenecks in the drug discovery process. There are many rodent models of pancreatic cancer, but most of these fails to recapitulate some of the key pathophysiological (pathological + physiological) aspects of the human disease. Although majority of biological processes are strikingly similar between humans and rodents, but rodents are NOT human!

This means that the best models for a human disease are the patients themselves. While experimental studies on human are strictly confined within the realm of clinical trials, patient’s own samples harbor immense potential in developing new diagnostic tests and ‘patient-derived model systems’ among other clinical applications. A successful establishment of the latter offers a unique and realistic possibility in predicting drug response using the cognate pathological tissue.

Researchers from the laboratory of Mikael Björnstedt from the Division of Pathology, Department of Laboratory Medicine, KI and collaborators have developed such a model system which could lead to new and improved treatment for pancreatic ductal adenocarcinoma, one of the major subtypes of pancreatic cancer.

In a recently published paper in Scientific Reports by Misra et al., the authors described development and validation of a model system, known as precision-cut organotypic slice culture. In this method, a small piece of tumor tissue is obtained from the freshly resected surgical specimen from pancreatic cancer patients. This small piece of tumor is then precisely cut into thin slices (350 µm) and cultured in the laboratory. The researchers developed a unique method in which these slices can be kept alive for at least 4 days - during which cancer cells proliferated, maintained their key morphological features and cellular markers and preserved their metabolic activities. The culture duration offers a reasonable window for drug testing. When these slices were treated with a pharmacological agent that inhibits a key metabolic pathway of cancer cells, anticipated cellular response was found. This suggests preservation of a key cellular pathway under investigation in a functionally active cancer tissue under laboratory condition.

Picture of Sougat Misra– It is an exciting development in the field of cancer model and drug development, says Sougat Misra who share the first authorship with Carlos F. Moro, a Ph.D. student and a clinical pathologist in the Laboratory for Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge. This 3D model system is by far the closest approximate of human pancreatic cancer outside of human body and amenable to manipulation without systemic intervention in patients. Essentially it is a ‘fingerprint’ of the cognate tumor tissue that contains all the cellular and acellular constituents in precise configuration and therefore, harbor great potential spanning ‘cancer drug development’ to ‘personalized medicine’.

– Right now, our goal is to use this model system to test a battery of cancer chemotherapeutics in this model system to identify the most efficient drug in relevance to clinical protocol. If we are successful in enumerating responses to a set of clinically relevant drugs prior to adjuvant therapy (chemotherapy after surgical resection), it can change the landscape of treatment for pancreatic cancer patients. We are cautiously optimistic!

Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma.
Misra S, Moro C, Del Chiaro M, Pouso S, Sebestyén A, Löhr M, et al
Sci Rep 2019 Feb;9(1):2133