Transcriptome based individualized therapy of refractory pediatric sarcomas: feasibility, tolerability and efficacy

Oncotarget
Bushra WeidenbuschStefan Burdach

Abstract

Survival rates of pediatric sarcoma patients stagnated during the last two decades, especially in adolescents and young adults (AYAs). Targeted therapies offer new options in refractory cases. Gene expression profiling provides a robust method to characterize the transcriptome of each patient's tumor and guide the choice of therapy. Twenty patients with refractory pediatric sarcomas (age 8-35 years) were assessed with array profiling: ten had Ewing sarcoma, five osteosarcoma, and five soft tissue sarcoma. Overexpressed genes and deregulated pathways were identified as actionable targets and an individualized combination of targeted therapies was recommended. Disease status, survival, adverse events (AEs), and quality of life (QOL) were assessed in patients receiving targeted therapy (TT) and compared to patients without targeted therapy (non TT). Actionable targets were identified in all analyzed biopsies. Targeted therapy was administered in nine patients, while eleven received no targeted therapy. No significant difference in risk factors between these two groups was detected. Overall survival (OS) and progression free survival (PFS) were significantly higher in the TT group (OS: P=0.0014, PFS: P=0.0011). Median OS was 8.83 v...Continue Reading

References

Oct 1, 1987·Cancer·S B LanskyD R Miller
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jun 24, 2000·Nature·D J Lockhart, E A Winzeler
Feb 7, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J NeuzilC Weber
Jan 31, 2002·Paediatric Drugs·Ewa KoscielniakJörn Treuner
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 31, 2005·Nucleic Acids Research·David S WishartJennifer Woolsey
Aug 22, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Guido PastoreEva Steliarova-Foucher
Aug 24, 2007·The Lancet Oncology·Arduino VerdecchiaUNKNOWN EUROCARE-4 Working Group
Oct 4, 2007·Human Molecular Genetics·Katherine S GarmanAnil Potti
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Apr 21, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm A SmithGregory H Reaman
Oct 6, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniel D Von HoffRobert Penny
Nov 12, 2010·Nucleic Acids Research·David CroftLincoln Stein
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
May 24, 2013·Clinical Epidemiology·Ernest K AmankwahDamon R Reed
Dec 7, 2013·Perspectives in Clinical Research·R Purushotham Naidu
Feb 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stefan Burdach
Jul 6, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Apostolia-Maria TsimberidouDonald Berry
Mar 26, 2015·Translational Lung Cancer Research·Bryan A Chan, Brett G M Hughes
Jul 17, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Konstantin AgelopoulosCarsten Müller-Tidow
Jul 21, 2015·Nature Medicine·Andrew J GentlesAsh A Alizadeh
Aug 1, 2015·Nature Reviews. Drug Discovery·Asher Mullard
Dec 19, 2015·The Lancet Oncology·Christophe Le TourneauMaud Kamal
Mar 20, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wendy ChangJaved Khan
Aug 2, 2016·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Barbara C WorstOlaf Witt
Apr 5, 2017·Journal of the National Cancer Institute·Carl E AllenUNKNOWN Pediatric MATCH Target and Agent Prioritization Committee
Jun 10, 2017·International Journal of Cancer. Journal International Du Cancer·Peter HorakStefan Fröhling
Jul 21, 2017·Nature·Paul A NorthcottPeter Lichter
Aug 11, 2017·Clinical Pharmacology and Therapeutics·Richard Simon

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Citations

Aug 14, 2019·Expert Opinion on Emerging Drugs·Claudia Maria HattingerMassimo Serra
Jul 2, 2020·OncoTargets and Therapy·Deepam PushpamBivas Biswas
Sep 2, 2018·Molecular and Cellular Pediatrics·Stefan E G BurdachKlaus-Michael Debatin
Sep 21, 2020·Seminars in Cancer Biology·Apostolia M TsimberidouRazelle Kurzrock

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Datasets Mentioned

BETA
GSE73166

Methods Mentioned

BETA
biopsy
biopsies
chips

Clinical Trials Mentioned

NCT02091141
NCT02813135

Software Mentioned

REACTOME
GraphPad prism
limma
R package preprocessCore
TARGETgene
EICESS
R
R package gplots
KEGG

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