A database of genetic information of more than 270 cancer models, encompassing 25 different childhood cancers, has just been made publicly available. Children’s Cancer Institute contributed 90 leukaemia models to this global effort.

This week in the United States, through the Baylor College of Medicine (Texas) and Nationwide Children’s Hospital (Ohio), a database of genetic information of more than 270 patient-derived xenograft (PDX) models, across 25 different childhood cancers, was made publicly available. Researchers worldwide can now access this resource to hunt for genetic vulnerabilities in these cancers that can be targeted with new drugs and treatments.

What is a PDX model?

A patient-derived xenograft model, or PDX for short, is a model system of living, growing cancer cells that have been derived directly from patient tumour tissue. PDX models are becoming increasingly important tools for preclinical drug testing. They enable researchers to test promising new drugs in the laboratory, and thus to prioritise which drugs to pursue in clinical trials.

The Pediatric Preclinical Testing Consortium (PPTC)

Children’s Cancer Institute is a world leader in the development of PDX models.  Since 2005, our Leukaemia Biology program, led by Professor Richard Lock, has been part of the Pediatric Preclinical Testing Consortium (PPTC), a US National Cancer Institute-funded initiative whose goal is to produce reliable preclinical drug testing data using paediatric cancer PDX models.

Professor Lock’s team is the leukaemia testing site for the PPTC, and is the only site outside the US. The team uses PDX models of acute lymphoblastic leukaemia (ALL) to evaluate preclinical efficacy of up to 10 new drugs and drug combinations each year, with those deemed effective put forward for clinical evaluation. This has led to a number of drugs being promoted to clinical trials. Just as importantly, testing has highlighted drugs ineffective against paediatric ALL, helping reduce the number of ineffective agents reaching the clinic.

 

a blood smear showing large leukaemia cells
ALL cells in blood

The Pediatric Preclinical Genomic Characterization Project

To most effectively interpret test results, comprehensive genomic characterisation of each PDX model is needed. With it, researchers can try to exploit specific genetic vulnerabilities with new targeted treatments. However, this genetic information has been lacking for some of the PDX models used by members of the PPTC. Which is where the new database comes in.

The Pediatric Preclinical Genomic Characterization Project was created to characterise those childhood cancer PDX models used by PPTC that lacked full genomic data.  The result is a database of genetic information of more than 270 PDX models across 25 different childhood cancers.

a child's hand with green ink fingerprints above it

Professor Lock and his team contributed 90 PDX models of childhood ALL to this combined effort, assisted by Australian Federal Government Department of Health funding awarded to  Zero Childhood Cancer in November 2017. This funding was to support the development of a preclinical testing platform for the Zero Childhood Cancer personalised medicine program for children with high-risk cancer. Sequencing of the remaining xenograft models was possible due to additional gift funds to the PPTC from Alex’s Lemonade Stand Foundation.

According to Professor Lock, “the Australian Federal Government Department of Health funding will vastly improve our capacity to identify new targets in childhood cancer to develop and test novel individualised treatments and help to cure the disease”.

Learn more about our preclinical evaluation of new therapies.

Images supplied by iStock

 



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