Tumor models developed in the lab could improve treatment for pancreatic cancer – sciencedaily

An international team of scientists created a three-dimensional (3D) model of pancreatic cancer tumor in the laboratory, combining a bioengineered matrix and cells derived from patients that could be used to develop and test targeted treatments.

In a new study published today in Nature Communication, researchers from the University of Nottingham, Queen Mary University in London, Monash University and Shanghai Jiao Tong University have created a multicellular 3D microenvironment that uses cells derived from patients to recreate the way whose tumor cells develop into pancreatic cancer and respond to chemotherapy drugs.

Pancreatic cancer is very difficult to treat, especially since there are no signs or symptoms until the cancer has spread. It may be resistant to treatment and the survival rate is poor compared to other cancers, with only a 5-10% survival rate five years after diagnosis.

The study was led by Professors Alvaro Mata from the University of Nottingham (UK), Daniela Loessner from Monash University (Australia) and Christopher Heeschen from Jiao Tong University in Shanghai (China). Dr David Osuna de la Peña, principal investigator of the project, said: “There are two main barriers to treatment for pancreatic cancer: a very dense matrix of proteins and the presence of highly resistant cancer stem cells (SCCs) which are involved. in relapse and metastasis. In our study, we designed a matrix where CSCs can interact with other cell types and behave together more like in the body, opening up the possibility of testing different treatments in a more realistic way. “

There is a need for improved 3D cancer models to study tumor growth and progression in patients and to test responses to new treatments. Currently, 90% of successful cancer treatments tested in preclinically fail in the early stages of clinical trials and less than 5% of oncology drugs succeed in clinical trials.

Preclinical testing relies primarily on a combination of two-dimensional (2D) cell cultures grown in the laboratory and animal models to predict responses to treatment. However, conventional 2D cell cultures fail to mimic key features of tumor tissue, and interspecies differences can result in the ineffectiveness of many successful treatments in animal hosts in humans.

Therefore, new experimental 3D cancer models are needed to better recreate the human tumor microenvironment and incorporate patient-specific differences.

Self-assembly is the process by which biological systems assemble several molecules and cells in a controlled manner into functional tissues. By harnessing this process, the team created a novel hydrogel biomaterial composed of multiple, yet specific, proteins found in pancreatic cancer. This mechanism of formation allows the incorporation of key cell types to create biological environments that can mimic the characteristics of a patient’s tumor.

Professor Mata adds: “The use of human cancer models is increasingly common in the development of treatments for the disease, but the turnaround time is a major obstacle to their implementation. We have designed a complete and adjustable ex vivo model of pancreatic ductal adenocarcinoma. (PDAC) by assembling and organizing key matrix components with cells derived from patients. The models exhibit patient-specific transcriptional profiles, SCC functionality and high tumorigenicity; overall, they provide a more relevant scenario than organoid and sphere cultures. More importantly, drug responses were better reproduced in our self-assembled cultures than in other models.

We believe this model comes close to the vision of being able to take tumor cells from patients in the hospital, incorporate them into our model, find the optimal cocktail of treatments for a particular cancer, and deliver it to the patient. – all in a short period of time. Although this vision of precision medicine to treat this disease is still a long way off, this research is a step towards its realization. “

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Materials provided by University of Nottingham. Note: Content can be changed for style and length.

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