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TRINITY RESEARCHERS DRIVE LUNG CANCER RESEARCH TOWARDS NON-ANIMAL MODELS

The research work of Dr Dania Movia and Prof Adriele Prina-Mello (Laboratory for Biological Characterisation of Advanced Materials (LBCAM), Trinity Translational Medicine Institute) is among those cited in a knowledge base developed by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and freely available to download here: https://data.jrc.ec.europa.eu/dataset/176d71e6-5082-4b29-8472-b719f6bda323).

EURL ECVAM is an integral part of the European Commission Joint Research Centre (JRC). The mandate of EURL ECVAM is specified in the EU legislation on the protection of animals used for scientific purposes, and includes a number of duties to advance the Replacement, Reduction and Refinement (the “Three Rs” principle) of animal procedures in research.

Early this year, EURL ECVAM has undertaken a study to review available and emerging non-animal models in the field of respiratory tract diseases, including lung cancer. As a result of such study, EURL ECVAM has produced a unique knowledge base that contains detailed descriptions of non-animal models that can be used for research on respiratory diseases, and for the development of new drugs and therapies. It is expected that the knowledge base will be of particular use to competent authorities in EU Member States to ensure that scientists have properly considered the use of non-animal models and methods in their research.

According to EURL ECVAM, over 21,000 abstracts from the scientific literature were screened to build the knowledge base. Of these, 284 publications were selected by EURL ECVAM to compile the knowledge base, for describing the most representative and innovative models in the field. Two articles published by Drs Movia, Prina-Mello and their collaborators were included in the selection.

“We’re delighted to include the innovative lung model developed by Trinity researchers in our knowledge base, which provides an overview of the state-of-the-art in human-based models applied in biomedical research” - comments the European Commission’s Joint Research Centre scientist Dr Laura Gribaldo - “Our review shows a clear trend in respiratory tract disease research. Scientists are looking more and more to sophisticated models such as organoids and microfluidic lung-on-a-chip devices than can capture more complex biology and disease pathways”.

Recreating lung cancer tissue and its drug responses outside the human body

The model developed by the Trinity researchers is formed by human lung cancer cells and human healthy lung fibroblasts. These two cell types are grown together in a three-dimensional fashion, to form a so-called tumoroid. The tumoroid is at the air-liquid interface, i.e. its apical side is in direct contact with air. This replicates the conditions in which lung cancer develops in the patient.

The tumoroid replicates multi-drug chemoresistance mechanisms and feedback activation signalling processes observed in lung cancer patients, and that are responsible for their poor

prognosis. Thus, the tumoroid provides a new human-relevant tool allowing for the efficacy screening of inhaled anti-cancer drugs.

“Non-animal methods looking at cancer are generally not informed by advances in non-cancer methods”, says Dr Dania Movia, senior research fellow at LBCAM – “The novelty of our model is that it fosters synergies from both field of cancer research and chemical safety assessment to create the first tumoroid grown at the air-liquid-interface.”

Why are non-animal models important in lung cancer research?

Lung cancer is more than ever a leading cause of cancer-related mortality worldwide, with more than 1.5 million deaths every year. On average, 2,502 people are diagnosed with lung cancer every year in Ireland. Patients’ prognosis is extremely poor. Although there are several reasons for this, limitations of animal models to capture critical aspects of human disease are being increasingly cited as a critical issue in the successful development of effective drugs against lung cancer. For example, inhaled drugs offer tremendous opportunities in the treatment of lung cancer. However, no inhaled anti-cancer drugs exist to date. The problem is, current preclinical models have critical limitations in predicting the behaviour and action of such treatments in patients.

The outlook in research is shifting therefore to non-animal, human-relevant models that can advance our understanding of lung cancer, our ability to develop effective therapies, and ultimately offer new hope to patients.

“The model we developed could support and guide the rational selection and screening for efficacy and safety of inhaled anti-cancer drug candidates and nanomedicines in the future” – comments Prof Prina-Mello, director of the LBCAM – “In the long-term, this model will reduce in vivo studies, accelerate pre-clinical translational screening where to maximise the impact of bringing new drugs to patients.”

Further information on this research

Movia, D., Bazou, D., Volkov, Y., Prina-Mello A. Multilayered Cultures of NSCLC cells grown at the Air-Liquid Interface allow the efficacy testing of inhaled anti-cancer drugs. Nature Sci Rep 8, 12920 (2018).

Can be viewed for free here: https://doi.org/10.1038/s41598-018-31332-6

Movia, D., Bazou, D. and Prina-Mello, A. ALI multilayered co-cultures mimic biochemical mechanisms of the cancer cell-fibroblast cross-talk involved in NSCLC MultiDrug Resistance. BMC Cancer 19, 854 (2019).

Can be viewed for free here: https://doi.org/10.1186/s12885-019-6038-x

About LBCAM:

The Laboratory for Biological Characterisation of Advanced Materials (LBCAM) is the innovative centre for material characterisation, biological interaction models development and pre-clinical assessment of biomedical solution or medical technologies for academic research groups and industry.

For any further information please contact us at:

Dr. D. Movia, contact email: dmoviaATtcd.ie

Dr. A. Prina-Mello, contact email: prinameaATtcd.ie