Syst-15 Generation and Multi-dimensional Profiling of a Childhood Cancer Cell Line Atlas Defines New Therapeutic Opportunities
Year: 2023
Type: conference-abstract
Abstract: Paediatric solid tumours are the leading cause of cancer related death amongst children. Identification of paediatric-specific targeted therapies necessitates the use of paediatric cancer models that faithfully recapitulate the patient’s disease. In adult cancers, comprehensive cell line repositories and data atlases have enabled both hypothesis-driven research and scalable screens for new therapies. The generation and characterisation of paediatric cancer cell lines has significantly lagged behind that of their adult counterparts, underscoring the urgent need to develop a paediatric-focussed cell line resource. Herein, we establish a single-site collection of 261 cell lines, including 224 paediatric cancer cell lines representing 18 distinct extracranial and brain childhood tumour types. We subjected 182 paediatric cancer cell lines to multi-omic analyses across three dimensions (DNA-sequencing, RNA-sequencing, DNA methylation) to classify them based on clinically relevant molecular subtypes. In parallel, pharmacological and genetic CRISPR-Cas9 loss of function screens were performed to identify paediatric-specific drug sensitivities and genetic dependencies. Machine-learning approaches were employed to delineate predictive features of therapeutic vulnerabilities in different subtypes of paediatric cancers. By integrating molecular features with functional genomic and pharmacological profiles, we demonstrate how therapeutic target-biomarkers pairs may be rapidly prioritised and advanced. Lastly, we provide cell line data and resources in an open access portal (vicpcc.org.au/dashboard) to support drug development efforts, clinical trial design, and personalised medicine approaches for paediatric cancers of greatest unmet medical need.
Source: Neuro-Oncology Advances
Authors: Paul Daniel, Claire Xin Sun, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Diana Carvalho, Phillip B Storm, Valerie Baubet, Leanne C Sayles, Elisabet Fernandez, Nataliya Zhukova, Matthew D Dun, Louise E Ludlow, Bryan Day, Brett W Stringer, Naama Neeman, Jeffrey A Rubens, Eric H Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I Fletcher, Paul G Ekert, Biljana Dumevska, David S Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Yin Yee Low, E Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E Cain, Ron Firestein
Institutions: Hudson Institute of Medical Research, Monash University, Children's Hospital of Philadelphia, Institute of Cancer Research, University of California System, University of Newcastle Australia, Murdoch Children's Research Institute, QIMR Berghofer Medical Research Institute, Johns Hopkins University, Bambino Gesù Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, UNSW Sydney, Children's Cancer Institute Australia, Sydney Children's Hospital, KK Women's and Children's Hospital, University of California, San Francisco, Stanford Medicine, Stanford University, Monash Children’s Hospital, Monash Health
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,371
OpenAlex ID: W4385584366