EMBO Molecular Medicine (Apr 2022)
In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer
- Loretta M S Lau,
- Chelsea Mayoh,
- Jinhan Xie,
- Paulette Barahona,
- Karen L MacKenzie,
- Marie Wong,
- Alvin Kamili,
- Maria Tsoli,
- Tim W Failes,
- Amit Kumar,
- Emily V A Mould,
- Andrew Gifford,
- Shu‐Oi Chow,
- Mark Pinese,
- Jamie I Fletcher,
- Greg M Arndt,
- Dong‐Anh Khuong‐Quang,
- Carol Wadham,
- Daniel Batey,
- Georgina Eden,
- Peter Trebilcock,
- Swapna Joshi,
- Stephanie Alfred,
- Anjana Gopalakrishnan,
- Aaminah Khan,
- Dylan Grebert Wade,
- Patrick A Strong,
- Elodie Manouvrier,
- Lisa T Morgan,
- Miriam Span,
- Jin Yi Lim,
- Roxanne Cadiz,
- Caitlin Ung,
- David M Thomas,
- Katherine M Tucker,
- Meera Warby,
- Geoffrey B McCowage,
- Luciano Dalla‐Pozza,
- Jennifer A Byrne,
- Federica Saletta,
- Andrew Fellowes,
- Stephen B Fox,
- Murray D Norris,
- Vanessa Tyrrell,
- Toby N Trahair,
- Richard B Lock,
- Mark J Cowley,
- Paul G Ekert,
- Michelle Haber,
- David S Ziegler,
- Glenn M Marshall
Affiliations
- Loretta M S Lau
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Chelsea Mayoh
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Jinhan Xie
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Paulette Barahona
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Karen L MacKenzie
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Marie Wong
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Alvin Kamili
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Maria Tsoli
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Tim W Failes
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Amit Kumar
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Emily V A Mould
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Andrew Gifford
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Shu‐Oi Chow
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Mark Pinese
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Jamie I Fletcher
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Greg M Arndt
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Dong‐Anh Khuong‐Quang
- Children’s Cancer Centre Royal Children’s Hospital Parkville Vic. Australia
- Carol Wadham
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Daniel Batey
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Georgina Eden
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Peter Trebilcock
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Swapna Joshi
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Stephanie Alfred
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Anjana Gopalakrishnan
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Aaminah Khan
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Dylan Grebert Wade
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Patrick A Strong
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Elodie Manouvrier
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Lisa T Morgan
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Miriam Span
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Jin Yi Lim
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Roxanne Cadiz
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Caitlin Ung
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- David M Thomas
- Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW Australia
- Katherine M Tucker
- Hereditary Cancer Centre Prince of Wales Hospital Randwick NSW Australia
- Meera Warby
- Hereditary Cancer Centre Prince of Wales Hospital Randwick NSW Australia
- Geoffrey B McCowage
- Cancer Centre for Children The Children’s Hospital at Westmead Westmead NSW Australia
- Luciano Dalla‐Pozza
- Cancer Centre for Children The Children’s Hospital at Westmead Westmead NSW Australia
- Jennifer A Byrne
- Children’s Cancer Research Unit Kids Research Westmead NSW Australia
- Federica Saletta
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Andrew Fellowes
- Peter MacCallum Cancer Centre Melbourne Vic. Australia
- Stephen B Fox
- Peter MacCallum Cancer Centre Melbourne Vic. Australia
- Murray D Norris
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Vanessa Tyrrell
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Toby N Trahair
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Richard B Lock
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Mark J Cowley
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Paul G Ekert
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Michelle Haber
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- David S Ziegler
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- Glenn M Marshall
- Children’s Cancer Institute, Lowy Cancer Centre UNSW Sydney Kensington NSW Australia
- DOI
- https://doi.org/10.15252/emmm.202114608
- Journal volume & issue
-
Vol. 14,
no. 4
pp. n/a – n/a
Abstract
Abstract Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high‐throughput drug screening (HTS) and patient‐derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high‐risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found. Screens also provided orthogonal proof of drug efficacy suggested by molecular analyses and negative results for some molecular findings. We identified treatment options across the whole testing platform for 70% of patients. Only molecular therapeutic recommendations were provided to treating oncologists and led to a change in therapy in 53% of patients, of whom 29% had clinical benefit. These data indicate that in vitro and in vivo drug screening of tumor cells could increase therapeutic options and improve clinical outcomes for high‐risk pediatric cancer patients.
Keywords