In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer
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, an...
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-12-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202114608 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Loretta M S Lau |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f2db646d5831450d847f4d18a36cdea2 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-f2db646d5831450d847f4d18a36cdea22025-08-20T03:43:14ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-12-0114411510.15252/emmm.202114608In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancerLoretta M S Lau0Chelsea Mayoh1Jinhan Xie2Paulette Barahona3Karen L MacKenzie4Marie Wong5Alvin Kamili6Maria Tsoli7Tim W Failes8Amit Kumar9Emily V A Mould10Andrew Gifford11Shu‐Oi Chow12Mark Pinese13Jamie I Fletcher14Greg M Arndt15Dong‐Anh Khuong‐Quang16Carol Wadham17Daniel Batey18Georgina Eden19Peter Trebilcock20Swapna Joshi21Stephanie Alfred22Anjana Gopalakrishnan23Aaminah Khan24Dylan Grebert Wade25Patrick A Strong26Elodie Manouvrier27Lisa T Morgan28Miriam Span29Jin Yi Lim30Roxanne Cadiz31Caitlin Ung32David M Thomas33Katherine M Tucker34Meera Warby35Geoffrey B McCowage36Luciano Dalla‐Pozza37Jennifer A Byrne38Federica Saletta39Andrew Fellowes40Stephen B Fox41Murray D Norris42Vanessa Tyrrell43Toby N Trahair44Richard B Lock45Mark J Cowley46Paul G Ekert47Michelle Haber48David S Ziegler49Glenn M Marshall50Children’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Centre, Royal Children’s HospitalChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyKinghorn Cancer Centre, Garvan Institute of Medical ResearchHereditary Cancer Centre, Prince of Wales HospitalHereditary Cancer Centre, Prince of Wales HospitalCancer Centre for Children, The Children’s Hospital at WestmeadCancer Centre for Children, The Children’s Hospital at WestmeadChildren’s Cancer Research Unit, Kids ResearchChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyPeter MacCallum Cancer CentrePeter MacCallum Cancer CentreChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyChildren’s Cancer Institute, Lowy Cancer Centre, UNSW SydneyAbstract 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.https://doi.org/10.15252/emmm.202114608drug screenpatient‐derived xenograftpediatric cancerprecision medicine |
| spellingShingle | 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 In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer EMBO Molecular Medicine drug screen patient‐derived xenograft pediatric cancer precision medicine |
| title | In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer |
| title_full | In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer |
| title_fullStr | In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer |
| title_full_unstemmed | In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer |
| title_short | In vitro and in vivo drug screens of tumor cells identify novel therapies for high‐risk child cancer |
| title_sort | in vitro and in vivo drug screens of tumor cells identify novel therapies for high risk child cancer |
| topic | drug screen patient‐derived xenograft pediatric cancer precision medicine |
| url | https://doi.org/10.15252/emmm.202114608 |
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