Lab grown tumor models could improve treatment for pancreatic cancer


Date:
September 24, 2021
Source:
University of Nottingham
Summary:
An international team of scientists have created a three-dimensional
(3D) pancreatic cancer tumour model in the laboratory, combining a
bioengineered matrix and patient-derived cells that could be used
to develop and test targeted treatments.



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


==========================================================================
In a new study published today in Nature Communications, researchers from
the University of Nottingham, Queen Mary University of London, Monash University and Shanghai Jiao Tong University have created a multicellular
3D microenvironment that uses patient-derived cells to recreate the way
tumour cells grow in pancreatic cancer and respond to chemotherapy drugs.

Pancreatic cancer is very difficult to treat, particularly as there are
no signs or symptoms until the cancer has spread. It can be resistant
to treatment and the survivial rate is low 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 Shanghai Jiao Tong University (China). Dr
David Osuna de la Pen~a, a lead researcher on the project, said: "There
are two main obstacles to treating pancreatic cancer -- a very dense
matrix of proteins and the presence of highly resistant cancer stem
cells (CSCs) that are involved in relapse and metastasis. In our study,
we have engineered a matrix where CSCs can interact with other cell
types and together behave more like they do in the body, opening the possibility to test different treatments in a more realistic manner."
There is a need for improved 3D cancer models to study tumour growth and progression in patients and test responses to new treatments. At present,
90% of successful cancer treatments tested pre-clinically fail in the
early phases of clinical trials and less than 5% of oncology drugs are successful in clinical trials.

Pre-clinical tests mostly rely on a combination of two-dimensional
(2D) lab grown cell cultures and animal models to predict responses
to treatment.

However, conventional 2D cell cultures fail to mimic key features of
tumour tissues and interspecies differences can result in many successful treatments in animal hosts being ineffective in humans.

Consequently, novel experimental 3D cancer models are needed to
better recreate the human tumour microenvironment and incorporate patient-specific differences.

Self-assembly is the process by which biological systems controllably
assemble multiple molecules and cells into functional tissues. Harnessing
this process, the team created a new hydrogel biomaterial made with
multiple, yet specific, proteins found in pancreatic cancer. This
mechanism of formation enables incorporation of key cell types to create biological environments that can emulate features of a patient's tumour.

Professor Mata adds: "Using models of human cancer is becoming more
common in developing treatments for the disease, but a major barrier to
getting them into clinical applications is the turnaround time. We have engineered a comprehensive and tuneable ex vivo model of pancreative
ductal adenocarcinoma (PDAC) by assembling and organising key matrix
components with patient-derived cells. The models exhibit patient-specific transcriptional profiles, CSC functionality, and strong tumourigenicity; overall providing a more relevant scenario than Organoid and Sphere
cultures. Most importantly, drug responses were better reproduced in
our self-assembled cultures than in the other models.

We believe this model moves closer to the vision of being able to take
patient tumour cells in hospital, incorporate them into our model, find
the optimum cocktail of treatments for a particular cancer and deliver
it back to the patient -- all within a short timeframe. Although
this vision for precision medicine for treating this disease is
still a way off, this research provides a step towards realising it." ========================================================================== Story Source: Materials provided by University_of_Nottingham. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Osuna de la Pen~a, D., Trabulo, S.M.D., Collin, E. et
al. Bioengineered
3D models of human pancreatic cancer recapitulate in vivo tumour
biology.

Nat Commun, 20212021 DOI: 10.1038/s41467-021-25921-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210924075555.htm

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